Skip to main content
Wiley Open Access Collection logoLink to Wiley Open Access Collection
. 2026 Jun 13;49(5):497–503. doi: 10.1111/jvp.70087

Comparative Pharmacokinetics of Gentamicin in Healthy Young‐Adult and Geriatric Horses

Michelle L Ceresia 1,2, Daniela Bedenice 1,✉, Andrew Gestrich 1, Caroline A McKinney‐Aguirre 1, Mary Rose Paradis 1, Iman Zaghloul 2
PMCID: PMC13552513  PMID: 42287236

ABSTRACT

Aging may modify the pharmacokinetic disposition and excretion of gentamicin, although drug dose adjustments in aged horses are uncommon in clinical practice. Since high‐dose, once daily dosing of gentamicin is considered therapeutically most effective, a comparative single‐dose study was conducted to evaluate the differences in pharmacokinetics between healthy young‐adult (5–10 years) and geriatric (≥ 25 years) horses receiving 6.6 mg/kg gentamicin intravenously. Blood samples were collected at designated time‐points following drug administration and frozen at −80°C until assayed by a validated immunoassay. Gentamicin plasma concentrations versus time plots were analyzed by noncompartmental analysis using commercial software (WinNonlin‐v8.4). Baseline physical examination and hematological parameters did not differ between age groups, except for a lower mean bodyweight in the geriatric group (477 ± 4 kg vs. 402 ± 6 kg). None of the pharmacokinetic parameters were statistically different between age groups. The oldest geriatric horse (41 years) had a longer half‐life and lower clearance of 5.3 h and 22.79 L/h, respectively, compared to a range of 1.39–2.56 h and 26.39–40.59 L/h for the remainder of the geriatric group (25–29 years). Further studies may be indicated in horses > 30 years old to determine if dose reduction is necessary in this population.

Keywords: age‐related, aminoglycoside, equine, geriatric, horse, pharmacokinetic

1. Introduction

Aged horses, defined as 20 years and older by the National Animal Health Monitoring System, account for approximately 11% of the overall equine population (CEAH 2018). With an increasing proportion of geriatric horses, it is vital to better understand the impact of aging on physiological processes and its effect on pharmacokinetics to minimize adverse drug reactions in older patients. In both humans and animals, advanced age has been shown to affect physiologic systems such as cardiac output, respiratory gas exchange, plasma protein binding, liver and kidney function, and the ratio of body water to adipose tissue (Boss and Seegmiller 1981; McKeever 2003). However, today, most equine pharmacokinetic studies are based on younger horse populations, which influences current dosing recommendations.

The aminoglycoside gentamicin has antimicrobial activity against most gram‐negative bacteria (Fraisse et al. 2014), and its efficacy is conventionally determined by peak plasma concentration to MIC ratios. Toxicities include renal and ototoxicity, and neuromuscular blockade. In humans, advancing age is a risk factor for aminoglycoside‐induced ototoxicity and renal toxicity, which are generally determined by length of drug exposure and trough concentrations, among other factors (Drusano et al. 2007; Godber et al. 1995; Lackey et al. 1996; Moore et al. 1987; Mueller and Boucher 2009; Triggs and Charles 1999). Clarke and colleagues thus conducted a single dose study evaluating age‐related pharmacokinetics of low‐dose (3 mg/kg) gentamicin in healthy horses. Horses were divided into 3 groups (< 10 years [1.5–9 years], 10–20 years [11–18 years], and > 20 years [21–30 years, median 23]), and blood samples were collected up to 8 h. The investigators found no difference in pharmacokinetic parameters between geriatric and younger horses receiving low‐dose gentamicin (Clarke et al. 1992). Since high‐dose, once daily dosing is considered therapeutically more effective, the safety of high‐dose gentamicin administration in aged horses requires further investigation.

Therapeutic protocols in people recommend reductions in dose and/or dosing frequency for patients > 65 or 70 years old (Koo et al. 1996; Triggs and Charles 1999) which corresponds to an approximate age of 25 years in horses with an expected lifespan of up to 40 years (Mauderly and Hahn 1982; Paradis 2002). However, considering the differences in physiological manifestations of aging between species (Koyanagi et al. 2014; Modric and Martinez 2011), empirical dose adjustments for geriatric animals cannot be extrapolated based on information in humans. As research in older geriatric horses (> 25 years) receiving high‐dose gentamicin is currently lacking, the current study evaluates the differences in aminoglycoside pharmacokinetics between young‐adult (5–10 years) and geriatric horses ≥ 25 years old, receiving a single, clinically employed dose of 6.6 mg/kg intravenous gentamicin. We hypothesized that plasma levels of gentamicin will remain higher for longer periods of time in geriatric versus young‐adult horses as reflected by reduced clearance, increased AUC and longer T1/2β.

2. Materials and Methods

All procedures were approved by the Institutional Animal Care and Use Committee of the Cummings School of Veterinary Medicine at Tufts University and completed following written owner consent. Animals: Twenty‐six client‐owned horses were health‐screened on the farm, prior to study enrollment, of which 10 older horses were excluded due to the presence of a heart murmur. The remainder were deemed clinically healthy based on history, physical examination, hematology, and serum chemistry analyses. Sixteen horses were ultimately enrolled, transported, and acclimated to the large animal hospital at Cummings School of Veterinary Medicine at Tufts University with eight animals in each age group (young‐adults 5–10 years old; geriatric animals ≥ 25 years). All horses were maintained on their routine concentrate diet and provided ad libitum water and timothy hay throughout the study period.

2.1. Gentamicin Administration and Sample Collection

The day prior to drug administration a jugular venous catheter (Milacath Short Term; Mila International Inc., Erlanger, KY, USA) was placed on each side of the neck using standard, aseptic technique. The following day, a single intravenous dose of 6.6 mg/kg gentamicin sulfate (100 mg/mL; Henry Schein, Dublin, OH, USA) was administered over 2 min via a dedicated jugular catheter. Blood samples (10 mL) were collected from the opposite catheter at times 0 (pre‐dose), 5, 15, 30, 45 min, 1, 2, 4, 6, 8, 12, 18, and 24 h after drug administration. To avoid dilution effects, 10 mL of heparinized blood were withdrawn from the catheter prior to each sample collection and subsequently returned to the horse. Catheters were flushed with heparinized 0.9% NaCl solution (Heparin Sodium Injection, USP, 1000 USP Units/mL, APP Pharmaceuticals LLC, Schaumburg, IL; in 0.9% Sodium Chloride Injection USP, Baxter Healthcare Corporation, Deerfield, IL; 1 mL heparin per 500 mL solution) after gentamicin administration and every 6 h until study completion. All samples were immediately placed into heparinized tubes (Vacuette NH Sodium Heparin, Greiner Bio‐One North America Inc., Monroe, NC), chilled on ice and centrifuged within 30 min of collection at 2000 g for 10 min at 4°C. Plasma was subsequently separated and stored at −80°C until analysis. An additional 2 mL of blood was taken from each animal at time 0 and at 24‐h to measure packed cell volume (PCV), total solids (TS), and serum creatinine (S cr). Free catch urine samples were collected for analysis (Urine dipstick parameters and specific gravity (USG)) at the beginning of the study, and all animals were monitored for adverse effects for 24 h following study completion.

2.2. Assay Validation and Sample Analysis

Heparinized equine plasma was used to validate a commercially available homogeneous particle‐enhanced turbidimetric immunoassay (QMS Gentamicin Immunoassay, Thermo Fisher Scientific, Waltham, MA) as previously described (Gestrich et al. 2018). The immunoassay was in clinical use for therapeutic drug monitoring at the Veterinary Clinical Laboratory at Tufts Cummings School. In short, gentamicin‐free equine plasma (dilution plasma) was assayed 3 times, and zero recovery was confirmed. Manufacturer‐provided gentamicin sulfate solution (Henry Schein, Dublin, OH, USA) was subsequently diluted in equine plasma using fixed volume pipettes to obtain three separate reference solutions of 100, 50, and 5 μg/mL (high, medium, and low concentrations). A single gentamicin concentration was analyzed 10 times to determine the precision of the assay. The need for dilution of study samples was expected to obtain concentrations within the assay's range of linearity of 0.3–10 μg/mL. Each gentamicin reference solution (100, 50, and 5 μg/mL) was therefore diluted to obtain 5 samples per concentration within the range of assay linearity. Subsequently, all study samples that required dilution were both diluted and assayed in duplicate, and the mean result was reported. The limit of drug quantification (LOQ) was 0.3 μg/mL and the limit of detection (LOD) was 0.2 μg/mL.

2.3. Pharmacokinetic Analysis

Non‐compartmental analyses of plasma gentamicin concentrations were performed using commercial pharmacokinetic software (Phoenix WinNonlin 8.4, Certara, Princeton, NJ). The area under the plasma concentration time curve (AUC0‐∞) and the area under the first moment curve (AUMC0‐∞) were determined using the trapezoidal method with extrapolation to infinity. The systemic clearance (CL) was calculated using the dose/AUC, and the mean residence time (MRT) was obtained from the ratio of AUMC0‐∞ to AUC0‐∞. The apparent steady state volume of distribution (V dss = CL * MRT) was calculated. The peak concentration (C peak) is the concentration 30 min after the completion of drug administration, which approximates the time of transition from the distribution to elimination phase (T 1/2α * 5) (Bauquier et al. 2015; Jones et al. 1998; Pedersoli et al. 1980; Swan et al. 1995) and was defined on the basis of convention in therapeutic drug monitoring protocols in the veterinary and human literature (30 min infusion followed by a 30 min concentration (C peak) to allow for end of distribution). (Jones et al. 1998; Moore et al. 1986).

2.4. Statistical Analysis

Hematological and urine analyses data were compared between groups using independent samples T‐test or Mann–Whitney U analysis, dependent upon data normality as measured by the Shapiro–Wilk test. Hematological and physical parameters pre‐ and post‐treatment were evaluated via paired samples T‐test or Wilcoxon rank test based on the normality of data distribution. The Levene's test for variance was used to compare the variability of pharmacokinetic parameters between age groups. All results are presented as mean ± SD or median, range. Statistical analyses were performed using specialized statistical software (IBM SPSS 22), with p < 0.05 considered significant.

3. Results

3.1. Analysis

The immunoassay utilizing photometric measurements was reproducible with a high recovery rate and intra‐assay variability of 1.7%. The intra‐sample variation of ≤ 3.5% was considered acceptable. The obtained mean recovery was 102%, 101%, and 101% for 5, 50, and 100 μg/mL gentamicin reference solutions, with acceptable 5%, 2.3%, and 4.1% coefficients of variation, respectively.

3.2. Baseline Characteristics

Young adult horses included 5 geldings, 2 mares, and 1 stallion, while the geriatric group consisted of 5 geldings and 3 mares. Baseline physical exam and hematological parameters did not differ between age groups with the exception of age and weight (Table 1). However, median body condition score (BCS) was comparable between groups (p = 0.209), ranging from lean (3/9) to moderate (5/9).

TABLE 1.

Baseline characteristics of young‐adult (5–10 years) and aged (≥ 25 years) horses.

Parameters Young‐adult horses Geriatric horses p
Sex
Male 6 5
Female 2 3
Breed 3 THB, 3 QH, 1 Irish Sport Horse, 1 Morgan 3 QH, 2 Welsh Pony, I THB, 1 SDB, 1 Arabian cross
Age (year) 7 [6–8] 26 [25–41] < 0.001
Weight (kg) 477 ± 38 402 ± 56 0.007
BCS 4 [3.5–5.5] 4 [2–5] 0.209
S cr (mg/dL) 1.41 ± 0.25 1.41 ± 0.36 1.0
BUN (mg/dL) 16 ± 3.4 19 ± 5 0.179
PCV (%) 38.1 ± 4.2 36.6 ± 2.9 0.418
TS (g/dL) 6.5 ± 0.53 6.85 ± 0.5 0.182
USG 1.035 ± 0.02 1.037 ± 0.01 0.823

Note: Data reported as mean ± SD or median [range].

Abbreviations: BCS, Body Condition Score; BUN, blood urea nitrogen; PCV, packed cell volume; QH, Quarter Horse; S cr, serum creatinine; SDB, standardbred; THB, thoroughbred; TS, total solids; USG, urine specific gravity.

The mean baseline S cr (serum creatinine; 1.41 ± 0.25 mg/dL vs. 1.41 ± 0.36 mg/dL, p = 1.00) and BUN (blood urea nitrogen; 16 ± 3.4 mg/dL vs. 19 ± 5 mg/dL, p = 0.179) values were not significantly different between young‐adult and geriatric animals. Two horses, one from each age group, were moderately positive for protein on urine dipstick analysis, despite a normal S cr and urine protein to creatinine ratio. No abnormal urine sediment was noted in any horse, and all samples were free of glucose. Baseline ACTH levels obtained in geriatric horses were either elevated (42–323 pg/dL) or equivocal (27–75 pg/dL) in 4 horses each, based on seasonal reference ranges. No adverse drug events were observed, and all horses remained clinically healthy throughout the study period. Single dose gentamicin administration had no significant effect on S cr or PCV in either group.

3.3. Pharmacokinetics

The plasma concentration‐time curves and pharmacokinetic parameters following administration of 6.6 mg/kg IV gentamicin in 8 young‐adult and 8 geriatric horses are represented in Figure 1 and Table 2. In Figure 1 the plasma concentration of gentamicin displayed a rapid drug distribution for both groups, followed by a slower elimination phase. The geriatric group showed a lower elimination slope, but this was not statistically different from young‐adults. None of the pharmacokinetic parameters differed significantly between age‐groups, except for the systemic clearance not adjusted for weight. In geriatric horses, there was an 11% reduction in the weight‐adjusted clearance, and the AUC0‐∞ in the geriatric group was 12.2% higher compared to young‐adult horses; however, this difference was not statistically significant. The mean measured concentration at 5 (C 5min), 30 (C 30min), and 60 (C 60min) minutes post dose was comparable between young‐adults and aged animals (61.03 ± 8.91 vs. 62.89 ± 8.93 mg/L; 31.69 ± 4.36 vs. 31.91 ± 2.23 mg/L; and 21.56 ± 2.49 vs. 22.07 ± 1.48 mg/L, respectively).

FIGURE 1.

FIGURE 1

Mean ± standard deviation plasma concentration‐time profile after single‐dose intravenous administration of gentamicin (6.6 mg/kg) to 8 healthy young‐adult (5–10 years) and 8 aged (≥ 25 years) horses. Inset shows the first 2 h post‐administration. This figure contains quantifiable concentrations only.

TABLE 2.

Pharmacokinetic parameters following a single intravenous 6.6 mg/kg gentamicin administration in healthy young‐adult (5–10 years) and geriatric (≥ 25 years) horses (n = 8 per group) using noncompartmental analysis.

Pharmacokinetic parameter Young‐adult horses Geriatric horses p
C 0 (mg/L) 74.2 ± 12.9 77.3 ± 14.6 0.67
AUClast (mg h/L) 78.6 ± 15.7 88.2 ± 11.6 0.19
AUC0‐∞ (mg h/L) 80.0 ± 16.0 89.8 ± 11.9 0.19
AUCext (%) 1.7 ± 0.7 1.8 ± 0.6 0.88
V ss (L) 79.0 ± 12.4 74.6 ± 13.7 0.52
λ z (h−1) 0.4 ± 0.2 0.3 ± 0.1 0.14
t ½λ (h) 1.9 ± 0.6 2.6 ± 1.3 0.20
AUMClast (mg·h2/L) 148.2 ± 59.4 209.1 ± 92.0 0.19
AUMC0‐∞ (mg·h2/L) 165.2 ± 66.9 237.8 ± 112.4 0.14
MRTlast (h) 1.8 ± 0.4 2.3 ± 0.7 0.10
MRT0‐∞ (h) 2.0 ± 0.4 2.6 ± 0.8 0.10
Cl (L/h) 40.4 ± 6.9 30.1 ± 5.7 0.01
Cl (mL/h/kg) 84.7 ± 15.1 75.1 ± 9.2 0.13
C 30min (mg/L) 31.7 ± 4.4 31.9 ± 2.2 0.90
T last (h) 10.0 ± 2.8 13.0 ± 4.7 0.14
C last (mg/L) 0.6 ± 0.3 0.5 ± 0.1 0.40

Note: Data are reported as mean ± standard deviation. Significance p < 0.05.

Abbreviations: AUC0‐∞, area under the plasma concentration time curve from 0 to infinity; AUCext, percent extrapolated of area under the plasma concentration time curve; AUClast, area under the plasma concentration time curve from 0 to last concentration; AUMC0‐∞, area under the first moment curve from 0 to infinity; AUMClast, area under the first moment curve from 0 to last concentration; C 0, initial concentration; CL, systemic clearance; C last, last quantifiable (0.3 mg/L) concentration; C peak, concentration at 30 min; MRT0‐∞, mean residence time from 0 to infinity; MRTlast, mean residence time from 0 to last concentration; t ½λ, elimination half‐life; T last, time to last quantifiable concentration; V ss, volume of distribution at steady state; λ z, elimination rate constant.

The mean time and concentration of the last quantifiable gentamicin concentration (LOQ = 0.3 mg/L) was 10.00 ± 2.83 vs. 13.00 ± 4.66 h and 0.56 ± 0.34 vs. 0.45 ± 0.13 mg/L for the young adult and geriatric population, respectively (Table 2). The timepoint of the last detectable drug concentration (LOD = 0.2 mg/L) for each horse ranged from 6 to 18 h in young adults and 12 to 24 h in aged horses. Only 1 of the 8 geriatric horses, a 41‐year‐old mare, had a detectable drug concentration at 24 h (0.3 mg/L).

4. Discussion

Age‐adjusted dosing recommendations for geriatric patients (> 25 years old) are currently lacking in equine practice, which may increase the risk for renal injury with use of potentially nephrotoxic medications. Young‐adult and geriatric horses in our study had similar serum creatinine concentrations, setting the expectation for similar gentamicin clearance between age groups. However, creatinine may not truly reflect their renal clearance. For example, serum creatinine may be low to normal in geriatric patients, due to a decreased muscle mass in older compared to young‐adult horses (McKeever 2003). This pharmacokinetic study, therefore, provides a clearer guideline for dose regimens based on patient age.

Our results did not support a need for dose‐adjustment of IV gentamicin in clinically healthy geriatric horses under 30 years of age. However, a previous study in healthy alpacas showed a significantly lower gentamicin clearance and associated, prolonged elimination half‐life and higher AUC in aged compared to young‐adult animals (Gestrich et al. 2018). Reduced drug clearance was similarly reported in humans after the age of 60–70 years (Triggs and Charles 1999) due to a decline in renal function. In our study, gentamicin pharmacokinetics did not differ significantly between healthy young‐adult and geriatric horses similar to prior work performed by Clarke et al. (1992), using a lower dose of 3 mg/kg gentamicin IV in 21–30 year old horses (median age: 23 years) (Clarke et al. 1992). Geriatric horses in our current study ranged from 25 to 29 years old, apart from one 41‐year‐old mare. The terminal half‐life for the 41‐year‐old horse was longer (5.3 h) and her clearance was slower (22.79 L/h), compared to a range of 1.4–2.6 h and 26.4–40.6 L/h respectively for the rest of the geriatric group.

Geriatric aging can be affected or categorized by chronological, physiological, functional or demographic age (Ireland 2016). According to Ireland and colleagues, the definition of geriatric covers a diverse age group that can span 40 years in humans. Because of this, the geriatric group in people is subcategorized, with “very old age” including those 85 years old or greater, based on demographic data. Similarly, horses over 30 years old may be considered “very old” based on survivorship data (Ireland 2016). Moreover, frailty (based on the Reported Edmonton Frail Scale) in humans (mean age 80 years) was reported to be an independent factor reducing the clearance of gentamicin by 12% (Hodiamont et al. 2022; Johnston et al. 2014). Currently, no published frailty scale has been established in horses. However, it is noteworthy that our 41‐year‐old horse with the lowest BCS (3/9) had a 27% reduction in gentamicin clearance compared to mean clearance of the remaining geriatric group. Further data may thus be needed in horses over 30 years old to determine if a dose reduction is indicated in patients that are frail and/or older than 30 years of age.

Peak mean gentamicin concentrations did not differ between geriatric (31.9 ± 2.2 mg/L) and young‐adult horses (31.7 ± 4.4 mg/L) in the current study, which showed similar initial drug concentrations and peak drug levels at 30 min and 1 h, compared to previous reports (Durham 2018; Magdesian et al. 1998; Swan et al. 1995; Wilson et al. 2023). Additionally, the AUC per dose in our young‐adult horses (12.12 ± 2.43 h/mL, AUC 80.01 ± 16.01 mg*h/mL; dose 6.6 mg/kg) was similar to previous studies, reporting 12.69 ± 2.27 h/mL (AUC 83.79 ± 14.97 μg*h/mL; dose 6.6 mg/kg) (Godber et al. 1995, sequence 1 of a double crossover) and 11.97 ± 2.39 h/mL (AUC 39.5 ± 7.9 μg*h/mL; dose 3.3 mg/kg) (Swan et al. 1995). The terminal half‐life (0.78 and 1.2 ± 0.3 h) and volume of distribution (0.115 ± 0.04 and 0.12 ± 0.015 L/kg) reported by both Godber et al. (1995), sequence 1 of a double crossover and Swan et al. (1995), respectively, were also in agreement with results in our young‐adult horses.

The premise for high‐dose, once‐daily aminoglycoside dosing is based on achieving a high maximum concentration (C max) to MIC ratio (8–10 or greater) to maximize drug efficacy and the extension of the post antibiotic effect (PAE), which allows for continuation of bacterial suppression when drug concentrations fall below the MIC (Moore et al. 1987; Mueller and Boucher 2009). Durham and colleagues reported on gram‐negative bacterial isolates collected from the Liphook Equine Hospital or ambulatory practices and found the majority to be susceptible with an MIC ≤ 1 μg/mL for gentamicin (Durham 2018). The established CLSI MIC breakpoint for gentamicin is ≤ 2 μg/mL for susceptible microorganisms, 4 μg/mL for intermediate, and ≥ 8 μg/mL for resistant pathogens (CLSI 2023). Bauquier and colleagues targeted peaks of 32–40 μg/mL (8–10 times the intermediate MIC) in hospitalized horses due to nosocomial bacterial resistance (Bauquier et al. 2015). Our data support that a dose of 6.6 mg/kg gentamicin, as used in our current study, would be efficacious in both geriatric and young‐adult healthy horses for susceptible bacteria.

Current literature (EUCAST, VetCAST) supported by modeling studies favor the use of free area under the curve 0 to 24 h/MIC (fAUC24/MIC) for concentration dependent drugs over fC max/MIC (Toutain et al. 2021). Therapeutic drug monitoring for dose adjustments for the individual patient thus focuses on determination of AUC, and/or peak and trough concentrations. However, troughs are evaluated primarily for risk of toxicity, not efficacy. It is notable that the time to the last detectable drug concentration ranged from 6 to 18 h in young adults and 12 to 24 h in our geriatric horses. The reported duration of the PAE for aminoglycosides is 2–6 h (range 1.2–12.8 h) based on animal models (Onufrak et al. 2016), and the dosing interval for aminoglycosides should not exceed the duration of drug concentration above the MIC plus the PAE (Leggett et al. 1989; Zhanel and Craig 1994). Contemporary modeling used to predict dosage regimens for concentration dependent drugs intrinsically takes the PAE into account.

Median body weight of horses in our geriatric group was significantly lower than in young adults (402 ± 56 vs. 477 ± 38 kg; p < 0.001), despite a comparable body condition score. In people, a significantly greater V dss and, thus, a longer elimination half‐life of aminoglycoside has been documented in patients with lower total body weight, lower serum albumin concentrations and advanced age (Etzel et al. 1992) However, no difference in V dss was observed between age groups in horses, despite a lower body weight of the geriatric group. The latter may thus be related to phenotypic differences between age groups, or a lower muscle mass in geriatric horses due to expected, age‐associated sarcopenia (McKeever 2003). In contrast to reports in humans (Etzel et al. 1992), median available albumin levels were similar between age groups (young 3.2 ± 0.15; geriatric: 3.06 ± 0.23; p = 0.22), further supporting the observed similarities in drug volume and half‐life of both groups. Consistent with our study, Clark et al. documented similar albumin concentrations [3.4, 3.3 and 3.2 g/dL, respectively] between three different age groups of horses [1.5–9 years, 11–18 years, 21–30 years] (Clarke et al. 1992). Additionally, gentamicin protein binding of less than 30% has been reported in foals and mares (Cummings et al. 1990). Similarly, Abo EL‐Sooud documented 7.98% ± 0.43% gentamicin protein binding in foals (EL‐Sooud 2003). However, to the author's knowledge gentamicin protein binding in geriatric horses has not been reported.

Study limitations included a small sample size and the primary inclusion of horses under 30 years old in the geriatric group, with the exception of one 41‐year‐old horse. In conclusion, no statistically significant differences in any of the pharmacokinetic parameters were observed between young‐adult and geriatric horses. A single 6.6 mg/kg intravenous dose of gentamicin achieved therapeutic blood concentrations against susceptible pathogens with an MIC ≤ 2 μg/mL in both healthy young‐adult and geriatric horses. However, further studies should be conducted to evaluate the pharmacokinetics of gentamicin in horses greater than 30 years old (very old age).

Author Contributions

Individual contributions include client recruitment, study preparation, and animal management (A.G., D.B., M.R.P.); design and sample collection (A.G., D.B., M.R.P., M.L.C.); clinical analyses and data interpretation (A.G., D.B., M.L.C.); pharmacokinetic analysis and data interpretation (I.Z., M.L.C.); scientific writing (M.L.C., I.Z., D.B., C.A.M.‐A.); study funding and review (M.R.P.).

Funding

This study was funded and conducted by the Dorothy Russell Havemeyer Foundation.

Ethics Statement

The study was approved by the Institutional Animal Care and Use Committee of Cummings School of Veterinary Medicine at Tufts University and completed following written owner consent.

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgements

We would like to sincerely thank Ms. Cheryl Stockman and Ms. Sarah Cass at Tufts Cummings School of Veterinary Medicine, as well as Daniel Buffum, Danielle Canaday, Alexandra Marini, and Fionna Chin (MCPHS University) for excellent technical assistance. Statistical consultation was provided by Robin Ruthazer at the Institute for Clinical Research and Health Policy Studies, BERD Center, Boston MA.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon request.

References

  1. Bauquier, J. R. , Boston R. C., Sweeney R. W., Wilkins P. A., and Nolen‐Walston R. D.. 2015. “Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin.” Journal of Veterinary Internal Medicine 29, no. 6: 1660–1666. 10.1111/jvim.13626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boss, G. R. , and Seegmiller J. E.. 1981. “Age‐Related Physiological Changes and Their Clinical Significance.” Western Journal of Medicine 135, no. 6: 434–440. [PMC free article] [PubMed] [Google Scholar]
  3. CEAH . 2018. Age‐Related Trends in Demographics of Equids in the United States. USDA and APHIS Veterinary Services. https://www.aphis.usda.gov/sites/default/files/equine15_is_trendsage.pdf. [Google Scholar]
  4. Clarke, C. R. , Lochner F. K., and Bellamy J.. 1992. “Pharmacokinetics of Gentamicin and Antipyrine in the Horse—Effect of Advancing Age.” Journal of Veterinary Pharmacology and Therapeutics 15, no. 3: 309–313. 10.1111/j.1365-2885.1992.tb01022.x. [DOI] [PubMed] [Google Scholar]
  5. CLSI . 2023. “Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals.” In CLSI Supplement VET01S. Clinical and Laboratory Standards Institute. [Google Scholar]
  6. Cummings, L. E. , Guthrie A. J., Harkins J. D., and Short C. R.. 1990. “Pharmacokinetics of Gentamicin in Newborn to 30‐Day‐Old Foals.” American Journal of Veterinary Research 51, no. 12: 1988–1992. [PubMed] [Google Scholar]
  7. Drusano, G. L. , Ambrose P. G., Bhavnani S. M., Bertino J. S., Nafziger A. N., and Louie A.. 2007. “Back to the Future: Using Aminoglycosides Again and How to Dose Them Optimally.” Clinical Infectious Diseases 45, no. 6: 753–760. 10.1086/520991. [DOI] [PubMed] [Google Scholar]
  8. Durham, A. E. 2018. “An Evaluation of Serum Gentamicin Concentrations and Bacterial Susceptibility to Gentamicin in Equine Practice.” Journal of Veterinary Internal Medicine 32, no. 3: 1194–1201. 10.1111/jvim.15078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. EL‐Sooud, K. A. 2003. “Comparative Disposition Kinetics and Plasma Protein Binding of Gentamicin Sulphate in Three Juvenile Animal Species.” Journal of Veterinary Medicine Series A 50: 196–200. 10.1046/j.1439-0442.2003.00530.x. [DOI] [PubMed] [Google Scholar]
  10. Etzel, J. V. , Nafziger A. N., and Bertino J. S. Jr. 1992. “Variation in the Pharmacokinetics of Gentamicin and Tobramycin in Patients With Pleural Effusions and Hypoalbuminemia.” Antimicrobial Agents and Chemotherapy 36, no. 3: 679–681. 10.1128/AAC.36.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fraisse, T. , Gras Aygon C., Paccalin M., et al. 2014. “Aminoglycosides Use in Patients Over 75 Years Old.” Age and Ageing 43, no. 5: 676–681. 10.1093/ageing/afu023. [DOI] [PubMed] [Google Scholar]
  12. Gestrich, A. , Bedenice D., Ceresia M., and Zaghloul I.. 2018. “Pharmacokinetics of Intravenous Gentamicin in Healthy Young‐Adult Compared to Aged Alpacas.” Journal of Veterinary Pharmacology and Therapeutics 41, no. 4: 581–587. 10.1111/jvp.12506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Godber, L. M. , Walker R. D., Stein G. E., Hauptman J. G., and Derksen F. J.. 1995. “Pharmacokinetics, Nephrotoxicosis, and In Vitro Antibacterial Activity Associated With Single Versus Multiple (Three Times) Daily Gentamicin Treatments in Horses.” American Journal of Veterinary Research 56, no. 5: 613–618. [PubMed] [Google Scholar]
  14. Hodiamont, C. J. , van den Broek A. K., de Vroom S. L., Prins J. M., Mathot R. A. A., and van Hest R. M.. 2022. “Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram‐Negative Infections: An Updated Review.” Clinical Pharmacokinetics 61, no. 8: 1075–1094. 10.1007/s40262-022-01143-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ireland, J. 2016. “Demographics, Management, Preventive Health Care and Disease in Aged Horses.” Veterinary Clinics of North America. Equine Practice 32: 195–214. [DOI] [PubMed] [Google Scholar]
  16. Johnston, C. , Hilmer S. N., McLachlan A. J., Matthews S. T., Carroll P. R., and Kirkpatrick C. M.. 2014. “The Impact of Frailty on Pharmacokinetics in Older People: Using Gentamicin Population Pharmacokinetic Modeling to Investigate Changes in Renal Drug Clearance by Glomerular Filtration.” European Journal of Clinical Pharmacology 70, no. 5: 549–555. 10.1007/s00228-014-1652-7. [DOI] [PubMed] [Google Scholar]
  17. Jones, S. L. , Wilson W. D., and Milhalyi J. E.. 1998. “Pharmacokinetics of Gentamicin in Healthy Adult Horses During Intravenous Fluid Administration.” Journal of Veterinary Pharmacology and Therapeutics 21, no. 3: 247–249. 10.1046/j.1365-2885.1998.00123.x. [DOI] [PubMed] [Google Scholar]
  18. Koo, J. , Tight R., Rajkumar V., and Hawa Z.. 1996. “Comparison of Once‐Daily Versus Pharmacokinetic Dosing of Aminoglycosides in Elderly Patients.” American Journal of Medicine 101, no. 2: 177–183. [DOI] [PubMed] [Google Scholar]
  19. Koyanagi, T. , Yamaura Y., Yano K., Kim S., and Yamazaki H.. 2014. “Age‐Related Pharmacokinetic Changes of Acetaminophen, Antipyrine, Diazepam, Diphenhydramine, and Ofloxacin in Male Cynomolgus Monkeys and Beagle Dogs.” Xenobiotica 44, no. 10: 893–901. 10.3109/00498254.2014.903532. [DOI] [PubMed] [Google Scholar]
  20. Lackey, M. N. , Belknap E. B., Greco D. S., and Fettman M. J.. 1996. “Single Intravenous and Multiple Dose Pharmacokinetics of Gentamicin in Healthy Llamas.” American Journal of Veterinary Research 57, no. 8: 1193–1199. [PubMed] [Google Scholar]
  21. Leggett, J. E. , Fantin B., Ebert S., et al. 1989. “Comparative Antibiotic Dose‐Effect Relations at Several Dosing Intervals in Murine Pneumonitis and Thigh‐Infection Models.” Journal of Infectious Diseases 159, no. 2: 281–292. 10.1093/infdis/159.2.281. [DOI] [PubMed] [Google Scholar]
  22. Magdesian, G. K. H. , Patricia M., Cohen N. D., Brumbaugh Gordon W., and Bernard W. V.. 1998. “Pharmacokinetics of a High Dose of Gentamicin Administered Intravenously or Intramuscularly to Horses.” Journal of the American Veterinary Medical Association 213, no. 7: 1007–1011. [PubMed] [Google Scholar]
  23. Mauderly, J. , and Hahn F.. 1982. “The Effects of Age on Lung Function and Structure of Adult Animals.” Advances in Veterinary Science and Comparative Medicine 26: 35–77. [PubMed] [Google Scholar]
  24. McKeever, K. H. 2003. “Aging and How It Affects the Physiological Response to Exercise in the Horse.” Clinical Techniques in Equine Practice 2, no. 3: 258–265. [Google Scholar]
  25. Modric, S. , and Martinez M.. 2011. “Patient Variation in Veterinary Medicine–Part II–Influence of Physiological Variables.” Journal of Veterinary Pharmacology and Therapeutics 34, no. 3: 209–223. 10.1111/j.1365-2885.2010.01249.x. [DOI] [PubMed] [Google Scholar]
  26. Moore, R. D. , Lietman P. S., and Smith C. R.. 1987. “Clinical Response to Aminoglycoside Therapy: Importance of the Ratio of Peak Concentration to Minimal Inhibitory Concentration.” Journal of Infectious Diseases 155, no. 1: 93–99. 10.1093/infdis/155.1.93. [DOI] [PubMed] [Google Scholar]
  27. Moore, R. D. , Smith C. R., and Lietman P. S.. 1986. “Response to Aminoglycoside Therapy—Importance of the Peak Plasma‐Level Mic Ratio.” Clinical Pharmacology & Therapeutics 39, no. 2: 213. [Google Scholar]
  28. Mueller, E. W. , and Boucher B. A.. 2009. “The Use of Extended‐Interval Aminoglycoside Dosing Strategies for the Treatment of Moderate‐to‐Severe Infections Encountered in Critically Ill Surgical Patients.” Surgical Infections 10, no. 6: 563–570. 10.1089/sur.2007.080. [DOI] [PubMed] [Google Scholar]
  29. Onufrak, N. J. , Forrest A., and Gonzalez D.. 2016. “Pharmacokinetic and Pharmacodynamic Principles of Anti‐Infective Dosing.” Clinical Therapeutics 38, no. 9: 1930–1947. 10.1016/j.clinthera.2016.06.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Paradis, M. R. 2002. “Demographics of Health and Disease in the Geriatric Horse.” Veterinary Clinics of North America. Equine Practice 18, no. 3: 391–401. 10.1016/s0749-0739(02)00021-4. [DOI] [PubMed] [Google Scholar]
  31. Pedersoli, W. M. , Belmonte A., Purohit R. C., and Ravis W. R.. 1980. “Pharmacokinetics of Gentamicin in the Horse.” American Journal of Veterinary Research 41, no. 3: 351–354. [PubMed] [Google Scholar]
  32. Swan, G. E. , Guthrie A. J., Mulders M. S., et al. 1995. “Single and Multiple Dose Pharmacokinetics of Gentamicin Administered Intravenously and Intramuscularly in Adult Conditioned Thoroughbred Mares.” Journal of the South African Veterinary Association 66, no. 3: 151–156. [PubMed] [Google Scholar]
  33. Toutain, P.‐L. , Pelligand L., Lees P., Bousquet‐Mélou A., Ferran A. A., and Turnidge J. D.. 2021. “The Pharmacokinetic/Pharmacodynamic Paradigm for Antimicrobial Drugs in Veterinary Medicine: Recent Advances and Critical Appraisal.” Journal of Veterinary Pharmacology and Therapeutics 44: 172–200. 10.1111/jvp.12917. [DOI] [PubMed] [Google Scholar]
  34. Triggs, E. , and Charles B.. 1999. “Pharmacokinetics and Therapeutic Drug Monitoring of Gentamicin in the Elderly.” Clinical Pharmacokinetics 37, no. 4: 331–341. 10.2165/00003088-199937040-00004. [DOI] [PubMed] [Google Scholar]
  35. Wilson, K. E. , Bogers S. H., Council‐Troche R. M., and Davis J. L.. 2023. “Potassium Penicillin and Gentamicin Pharmacokinetics in Healthy Conscious and Anesthetized Horses.” Veterinary Surgery 52, no. 1: 87–97. 10.1111/vsu.13896. [DOI] [PubMed] [Google Scholar]
  36. Zhanel, G. G. , and Craig W. A.. 1994. “Pharmacokinetic Contributions to Postantibiotic Effects. Focus on Aminoglycosides.” Clinical Pharmacokinetics 27, no. 5: 377–392. 10.2165/00003088-199427050-00005. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon request.


Articles from Journal of Veterinary Pharmacology and Therapeutics are provided here courtesy of Wiley

RESOURCES