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. 2025 Jun 12;48(6):491–497. doi: 10.1111/jvp.70006

Pharmacokinetics of Single Dose and Multidose Oral Gabapentin in Goats (Capra aegagrus hircus)

Jessie C Ziegler 1,✉, Meera Heller 2, Sherry Cox 3, Joe S Smith 4
PMCID: PMC12598904  PMID: 40503698

ABSTRACT

There is a shifting public perception of animal welfare that has increased demand for establishing pain management strategies in livestock. Gabapentin is often utilized in practice to mitigate neuropathic pain. However, there is little pharmacokinetic information to guide its use in goats. The objectives of this study were to describe the pharmacokinetics of oral gabapentin in goats given as a single dose (SD) and multidose (MD) regimen, as well as to document any adverse effects after administration. Six healthy adult goats were administered 15 mg/kg of gabapentin orally once for the SD trial, and every 12 h for 6 doses for the MD trial. Plasma samples were collected and analyzed via reversed‐phase high‐performance liquid chromatography. After SD administration, maximum plasma concentration, time to maximum concentration, and elimination half‐life were: 3.22 μg/mL; 4.49 h; and 8.15 h, respectively. After MD administration, maximum plasma concentration and time to maximum concentration were: 4.56 μg/mL and 2.24 h. Accumulation ratio (R) was 1.66 ± 0.81 when comparing the MD AUC12h to the SD AUC12h. Clinicians should be aware of the potential for increased accumulation ratio with multiple dosing strategies.

Keywords: gabapentin, goat, pharmacokinetics

1. Introduction

Shifting public perception of animal welfare has fueled reassessment of pain management strategies used in livestock animals (Alonso et al. 2020). Additionally, goats are becoming more popular in the USA as pets and companion animals (“Chew on This: Goats as Pets,” 2020), which increases the need for easily administered treatments for chronic painful conditions of geriatric animals.

Pathologic pain can be due to tissue damage, nerve damage, or inflammation (Coetzee et al. 2011). While inflammatory pain will respond to non‐steroidal anti‐inflammatories and opioids, neuropathic pain is refractory to them (Coetzee et al. 2011; Malreddy et al. 2013). There is a need to identify new treatments for use in goats to help treat chronic and neuropathic pain, as well as treatments that can be utilized in multi‐modal approaches to pain management. Gabapentin is an analogue of the neurotransmitter ɣ‐aminobutyric acid (GABA) that is an effective analgesic for inflammatory and chronic pain of a neuropathic origin (Coetzee 2013; Coetzee et al. 2011; Hurley et al. 2002). Gabapentin is not labeled for use in goats but is often prescribed as an extra‐label treatment for chronic pain. There is limited scientific information regarding pharmacokinetics in goats; thus, current dosing recommendations in goats are extrapolated from other species. Dosing is generally recommended at 10–20 mg/kg every 8–24 h in horses, dogs, and cats (Adrian et al. 2018; Gold et al. 2022; KuKanich and Cohen 2011). In ruminant beef calves, a single oral dose of gabapentin alone (10 mg/kg), or co‐administered (15 mg/kg) with 0.5 mg/kg meloxicam orally, reaches minimum therapeutic plasma concentrations (2 μg/mL) reported for humans for up to 15 h (Coetzee et al. 2011; Sivenius et al. 1991). A recent study in goats, evaluating a single 15 mg/kg oral dose of gabapentin, found that maximum plasma concentrations in 4 out of 6 animals were below minimum therapeutic concentrations established for humans (Kleinhenz et al. 2024; Sivenius et al. 1991). It is important to note that the minimally effective therapeutic concentration for cattle or goats has not been determined (Coetzee et al. 2011; Kleinhenz et al. 2024).

In practice, gabapentin is used to treat chronic pain; therefore, it is prescribed to be given in multiple doses over a prolonged period of time. The pharmacokinetics of a single oral dose have been described in beef calves, dairy cows, and goats, but there is no data on oral multi‐dosage administration in goats (Coetzee et al. 2011; Kleinhenz et al. 2024; Malreddy et al. 2013). Moreover, in humans, it takes a few weeks for gabapentin to reach full effect in treating neuropathic pain, further highlighting the need to study multi‐dose administration in goats (Chincholkar 2020).

Currently, there is insufficient data for the use of gabapentin in goats when prescribing multiple doses or recommending withdrawal intervals. The objectives of this study were to describe the pharmacokinetics of oral gabapentin in goats given as a single dose (SD) and multidose (MD) regimen, as well as document any adverse effects of oral MD gabapentin in goats.

2. Materials and Methods

2.1. Animals

Six adult, non‐lactating, female Alpine and Saanen goats from a university teaching and production herd were used for this study. They ranged from 18 to 24 months in age, and their body weights ranged from 52 to 65 kg at enrollment. This study was done in two phases, SD and MD, with a 3‐week washout period in between. Prior to enrollment for each phase, all animals received a complete physical exam by a board‐certified large animal internist and were weighed; animals showing any signs of illness upon physical exam were not enrolled. During each trial, goats were manually restrained by an experienced handler for gabapentin administration, blood sample collection, and daily physical exams. All study procedures were approved by the Institutional Animal Care and Use Committee at UC Davis (protocol # 22828).

The goats were housed as a group on concrete flooring with straw bedding and access to an outside area. They were fed alfalfa hay twice daily, at a level that met or exceeded the National Research Council's nutritional recommendations for goats (National Research Council 2007). The feeding schedule was not modified during the study protocol to mimic typical drug administration practices by veterinarians and owners.

2.2. Drug Administration and Blood Collection

For the SD phase, goats received a single dose of 15 mg/kg of Gabapentin via nasogastric tube. The gabapentin capsules (Amneal Pharmaceuticals, Bridgewater, NJ, USA) were opened and each individual dose was weighed into 50 mL conical tubes (Corning Corporation, Glendale, AZ, USA) to obtain accurate dosages for each animal. Immediately prior to administration, the gabapentin doses were mixed with 60 mL of water and administered via the nasogastric tube, followed by 120 mL of water to clear the tube prior to removal. Nasogastric tube placement within the rumen was confirmed by blowing into the tube while auscultating over the rumen using a stethoscope. Blood samples were collected just prior to administration and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, and 144 h after administration via jugular venipuncture into 10 mL heparinized Vacutainer tubes (Becton Dickinson, Franklin Lakes, NJ, USA). Blood was immediately centrifuged at 3000 g for 10 min. The plasma was collected into 1.5 mL aliquots and frozen at −20°C. Samples were moved to −80°C freezer within 48 h for storage and analyzed within 1–3 weeks.

The MD phase occurred after a 3‐week washout period, and the same goats were used for this part of the study. For the MD phase of the study, 15 mg/kg of gabapentin was administered orally every 12 h for 3 days, for 6 doses total. Each individual dose was prepared as above. Immediately prior to each dose administration, the pre‐weighed dose was suspended in 50 mL of warm water and administered orally using a 50 mL drench syringe (Cotran Corporation, Portsmouth, RI, USA). This route of administration mimics how oral medications are typically administered in a clinical setting. Blood samples were collected just prior to each dose and following the final (6th) dose at 0.25, 0.5, 1, 2, 4, 8, 12, 36, 60, 84, 108, 132, and 156 h after administration. Blood was subsequently processed and stored following phase 1 procedures.

2.3. Analysis of Plasma

Analysis of gabapentin in plasma samples was conducted using reversed‐phase HPLC. The system consisted of a 2695 separations module and a 2475 fluorescence detector (Waters, Milford, MA, USA.). Separation was attained on a Waters Atlantis T3 4.6 × 250 mm (5 μm) preceded by a 5 μm Atlantis T3 guard column. The mobile phase was a mixture of (A) 25 mM potassium phosphate dibasic buffer (pH 4.6) and (B) acetonitrile. The mixture was pumped at a starting gradient of 53% A and 47% B, adjusted to 49% A and 51% B over 15 min, then returned to initial conditions over 5 min. The flow rate was 1.1 mL/min. The fluorescence detector was set at an excitation of 300 and an emission of 500 with the gain at 10×.

Gabapentin was extracted from plasma samples using solid phase extraction (SPE; Mercolini et al. 2010). Previously frozen plasma samples were thawed and vortex‐mixed, after which 100 μL were transferred to a clean tube to be combined with 60 μL of internal standard (pregabalin 1 μg/mL) followed by 1 mL of 0.1 N HCl. This mixture was loaded onto a preconditioned MCX 1 cc cartridge (Waters). Samples were eluted with 2 mL of 10% ammonia in isopropyl alcohol and evaporated to dryness with nitrogen gas. Samples were re‐dissolved in 100 μL of water and subjected to the derivatization process.

Standard curves for plasma analysis were prepared by spiking untreated plasma with gabapentin, which produced a linear concentration range of 25–10,000 ng/mL. Average recovery was 87% for gabapentin. The quality control (QC) concentrations used were 75, 350, 3500, and 8000 ng/mL. The accuracy of the assay was within 100%, 95%, 101%, and 100%. The precision of the assay was (expressed as CV%) 0.4%, 1.2%, 4.0%, and 6.4%. The lower limit of quantification was 25 ng/mL.

2.4. Pharmacokinetic Analysis

Pharmacokinetic analysis of gabapentin concentrations was conducted using PKAnalix 2023R1 (Lixsoft, Antony, France). A noncompartmental extravascular administration model was used for analysis, with at least 3 concentration–time points used to calculate elimination rate (λz). The maximum plasma concentration (C max), time to achieve maximum plasma concentration (T max), elimination half‐life (T 1/2λz), mean residence time (MRT), area under the concentration–time curve at the last measured time with concentrations greater than the lower limit of quantification (AUClast), area under the concentration–time curve extrapolated to infinity (AUCinf), area under the concentration‐time curve for the first 12 h (AUC12), percent area under the concentration‐time curve extrapolated (%AUC), and area under the moments curve extrapolated to infinity (AUMCinf) were calculated using individual subject gabapentin concentrations.

Accumulation ratio (R) after multiple dosing was calculated according to the following formula:

R=AUCMD12hAUCSD12h

Where AUC(MD)12h corresponds to the area under the curve from 0 to 12 h after the last dose of the multiple dosing regimen and AUC(SD)12h corresponds to the area under the curve from 0 to 12 h after the single dosing regimen. Individual accumulation ratios were determined for each goat and then averaged.

3. Results

3.1. Animals

All goats tolerated drug administration and blood collection well. No adverse effects were noted with oral administration of gabapentin, aside from apparent mild sedation in one goat during the MD study, which resolved by 12 h following the final dose.

3.2. Pharmacokinetics

Time vs. Plasma concentration for both the SD and MD studies are outlined in Figures 1 and 2, respectively. Individual goat SD and MD time vs. concentration is displayed in Figure 3A,B, respectively. The mean pharmacokinetic parameters for the SD and MD studies are summarized in Tables 1 and 2, respectively. No gabapentin concentrations were detected after 48 h in any goat after SD administration. After MD administration, detectable levels were noted in all goats 144 h after the last administration. The accumulation ratio (R) was 1.66 ± 0.81 when comparing the MD AUC12h to the SD AUC12h.

FIGURE 1.

FIGURE 1

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Time vs. concentration data for gabapentin (square) after single oral dose administration (15.0 mg/kg) in adult goats (n = 6). Arithmetic mean concentration (ng/mL) is represented at each time point as a square with the upward bars representing standard error.

FIGURE 2.

FIGURE 2

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Time vs. concentration data for gabapentin (square) after oral administration (15.0 mg/kg) every 12 h for 6 doses in adult goats (n = 6). Arithmetic mean concentration (ng/mL) is represented at each time point as an open square. Multiple dosing occurred starting at time 0; as well as immediately after 12, 24, 36, 48 (blue boxes) with the last dose being administered at 60 h (gold box).

FIGURE 3.

FIGURE 3

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Individual time vs. concentration data for oral administration of gabapentin (15 mg/kg) after single dose (“A”) or multiple dosing (“B”; every 12 h for 6 doses) in adult goats (n = 6). Time vs. concentration information is presented as individual lines for each animal for single dose administration (A); and multiple dose administration (B).

TABLE 1.

Pharmacokinetic parameters (mean ± Standard Deviation; geometric mean unless indicated otherwise) for gabapentin after a single oral dose administration (15.0 mg/kg) in adult goats (n = 6).

Parameter Unit Mean (±SD) Minimum Maximum
C max μg/mL 3.22 ± 1.77 2.23 6.96
T max h 4.49 ± 1.63 (median: 4) 4 8
AUClast h*μg/mL 43.68 ± 11.51 32.85 61.04
AUCinf h*μg/mL 45.34 ± 13.58 33.56 66.39
AUC12 h*μg/mL 25.76 ± 9.0 19.00 43.1
%AUCext % 1.46 ± 5.30 0.26 14.18
AUMCinf h2*μg/mL 486.63 ± 176.69 362.04 832.11
MRT h 11.14 ± 2.08 9 14.6
λz 1/h 0.081 ± 0.029 0.043 0.13
T 1/2 λz a h 8.15 ± 3.68 5.21 14.6
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Abbreviations: λz, Elimination rate; %AUCext, percentage of area under the curve to infinity that is extrapolated; AUC12, Area under the curve calculated to 12 h after administration; AUCinf, Area under the curve extrapolated to infinity; AUClast, Area under the curve to the last time point; AUMCinf, Area under the moments curve extrapolated to infinity; C max, Maximum plasma concentration; MRT, Mean residence time; T 1/2 λz, Elimination half‐life; T max, Time to maximum plasma concentration.

a

Harmonic mean.

TABLE 2.

Pharmacokinetic parameters (mean ± SD; geometric mean unless indicated otherwise) for gabapentin after 6 oral dose administrations (15.0 mg/kg, q 12 h) in adult goats (n = 6).

Parameter Unit Mean (±SD) Minimum Maximum
C max μg/mL 4.563 ± 2614 1.809 9.373
T max h 2.24 ± 1.51 (median: 3) 1 4
AUClast h*μg/mL 147.22 55.51 138.65
AUCinf h*μg/mL 190.02 ± 283.15 67.88 766.07
AUC12 h*μg/mL 38.34 ± 26.68 12.82 85.75
%AUCext % 9.17 ± 18.4 1.93 46.5
AUMCinf h2*μg/mL 14,332 ± 56,948 3321 142,580,002
MRT h 75.42 ± 61.3 32.6 186.1
λz 1/h 0.000013 ± 0.0000078 0.000006 0.000025
R % 166.0 ± 81.0 61.0 301.0
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Note: Time zero for the multidose administration would be hour 60 of the entire study.

Abbreviations: λz, Elimination rate; %AUCext, percentage of area under the curve to infinity that is extrapolated; AUC12, Area under the curve calculated to 12 h after administration; AUCinf, Area under the curve extrapolated to infinity; AUClast, Area under the curve to the last time point; AUMCinf, Area under the moments curve extrapolated to infinity; C max, Maximum plasma concentration; MRT, Mean residence time; R, Accumulation ratio after multiple dosing when comparing the MD AUC12h to the SD AUC12h T max, Time to maximum plasma concentration.

4. Discussion

In this study, the PK parameters of gabapentin administered orally in a SD and MD regimen in adult dairy goats are described. A secondary goal of the study was to report any adverse effects from SD or MD administration in goats; however, the only clinically observable effect was mild sedation in one goat during the MD study. No ataxia was noted in our study, which has been previously reported with IV administration of gabapentin in goats (Costa et al. 2024).

The plasma concentrations of gabapentin in the study goats reached the comparative human therapeutic threshold of 2 μg/mL in both the SD and MD study when administered a 15 mg/kg oral dosage; similar to what has been reported for other species (Coetzee et al. 2011; KuKanich and Cohen 2011). The maximum plasma concentrations achieved with a single dose (3.22 μg/mL) are similar to those in calves administered 15 mg/kg PO (2.7–4.1 μg/mL; Fraccaro et al. 2013), as well as calves administered 10–15 mg/kg PO (2.97–3.57 μg/mL; Coetzee et al. 2011), but are higher than levels recently found in a study performed in goats administered 15 mg/kg (1.21–3.03 μg/mL) orally (Kleinhenz et al. 2024). The maximum plasma concentrations documented in the SD phase were similar to horses administered 20 mg/kg PO (3.75 μg/mL; Terry et al. 2010), although lower than dogs administered 20 mg/kg PO (KuKanich and Cohen 2011).

Table 3 lists comparative pharmacokinetic parameters for gabapentin after oral and intravenous administration at various doses in goats. Interestingly, when calculated as for SD, the MD T 1/2 was over 5‐fold longer than the SD T 1/2 (45.8 h and 8.15 h respectively). However, this is likely an artifact of the last sample collection time. For example, in Figure 3B, goats 1 (red) and 6 (orange) both have increasing concentrations at the last sampling time point. This could be due to the dissolved drug in the rumen being a reservoir for delayed absorption, or potentially enterohepatic recirculation. This is similar to goats 2 (green), 3 (blue), and 4 (purple), which also have concentrations that mildly increase then decrease in the terminal elimination phase. These increases can complicate the determination of elimination half‐life. However, the MD accumulation ratio of 1.66 suggests accumulation of gabapentin with multiple doses, which should be considered when recommending withdrawal intervals and dosing strategies.

TABLE 3.

Comparison of the PK parameters reported from veterinary literature and the caprine subjects of this study.

Parameter Unit Current study‐single dose Current study‐multi dose Kleinhenz et al. (2024) Costa et al. (2024) Costa et al. (2024)
Dose; Route mg/kg 15 (single); PO 15 (multiple dose); PO 15; PO 10; IV 10; PO
Formulation NA Dissolved Capsule (Oral Syringe) Dissolved Capsule (nasogastric tube) Capsules placed into a gelcap (balling gun) Compounded solution (intravenous catheter) Dissolved capsules (orogastric)
C 0/C max μg/mL 3.22 4.56 1.90 59.761 1.199
AUCinf h*μg/mL 45.34 28.29 43.1 40.369 23.895
MRT0–inf h 11.14 75.42 20.1 1.874 16.41
T max h 4.49 2.24 8 NA 6.862
T 1/2 h 8.15 45.8 9.4 1.8 8.2
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Abbreviations: AUCinf, Area under the curve extrapolated to infinity; C 0, Maximum calculated plasma concentration after IV administration; C max, Maximum plasma concentration; T 1/2 λz, Elimination half‐life; MRT0–inf, Mean residence time extrapolated to infinity; T max, Time to maximum plasma concentration.

It is possible that the accumulation in our study could be due to the route of administration, with the rumen/gastrointestinal tract serving as a reservoir for prolonged absorption, which extends into the elimination phase of the drug. This is supported by a recent study that showed SD oral administration of gabapentin in goats had a longer elimination half‐life than IV administration (Costa et al. 2024). It was concluded that the longer half‐life was likely due to prolonged absorption throughout the caprine gastrointestinal tract. Figure 3B shows that absorption continues beyond 120 h after the final dose administration in some individuals, as evidenced by the terminal (156 h) samples of goats 1 and 6, which showed increased concentrations compared to the 132 h samples, and increased concentrations in goats 2 and 3 in the 192 h and 168 h samples, respectively. The prolonged elimination half‐life observed after the MD phase could also result from the mathematical calculation of elimination based on increasing concentrations, and as such could be considered an artifact of the pharmacokinetic modeling process.

The pharmacokinetics in the SD component of our study had several differences when compared to the SD pharmacokinetic study conducted by Kleinhenz et al. (2024). While the present study found similar AUCinf values (45.34 h*μg/mL) compared to the Kleinhenz study (43.1 h*μg/mL), maximum concentrations were higher (3.22 μg/mL compared to 1.90 μg/mL) and a elimination half‐life was shorter (8.15 h compared to 9.4 h; Kleinhenz et al. 2024). Although the present study identified a wider range in elimination half‐lives (5.21–14.6 h) than the Kleinhenz study (6.1–11.5 h) the overlap between these ranges suggests marginal differences in elimination that may be due to differences in administration formulation. The Kleinhenz study administered intact gabapentin capsules orally inside a larger gelatin capsule rather than drug dissolved in water and administered via a nasogastric tube. Nasogastric tube administration of dissolved gabapentin could alter the rate of absorption compared to the capsules administered in gelcaps but would not be expected to affect the extent of absorption. A recent study (Costa et al. 2024) showed gabapentin in capsules failed to dissolve in ex vivo rumen fluid samples (pH of 7.5) within 96 h. It is possible that the Kleinhenz study's administration of the capsules served as a ‘sustained’ release mechanism thereby causing prolonged absorption. Similarly, while our reported accumulation ratio suggests accumulation after multiple dosing, the differences in administration may alter accumulation within the gastrointestinal tract, serving as a reservoir for continued absorption. Clinicians should note that administration after dissolution in water and administration by a tube could lead to higher plasma concentrations of gabapentin in goats.

Limitations of this study include having a small group of experimental subjects, of relatively uniform age and breed, which may limit the applicability of the data across a wider range of breeds. Pharmacokinetic studies are appropriately powered with 4–6 individual subjects (Riviere and Chittenden 2011). For the SD study, Gabapentin was administered via nasogastric tube, which may alter absorption compared to gabapentin offered with food, in capsules, or with a dosing syringe, as was done in the MD study. While administration with a dosing syringe in the MD is more in line with clinical administration, there was potential for drug loss during administration as compared with nasogastric administration. Drug administration, as mentioned above, could be responsible for the differences in PK parameters described by other studies; however, breed or age of the goats could also contribute. Oral gabapentin shows variable bioavailability in humans (Gidal et al. 2000).

Currently there is no established effective dose of gabapentin in goats. Additionally, while gabapentin can be administered as a single agent, it is commonly administered with a nonsteroidal anti‐inflammatory drug (NSAID), as human studies suggest a synergistic relationship for anti‐nociceptive stimuli (Hurley et al. 2002). The coadministration is described for cattle as well as small ruminants (Coetzee et al. 2011; Smith et al. 2021). However, it is currently unknown how the co‐administration of gabapentin with an NSAID could impact the pharmacokinetics or pharmacodynamics of either drug in the goat. Future studies could also utilize non‐linear mixed effect modeling to account for population variability (Bon et al. 2018). Due to the accumulation ratio noted in this study, less frequent dosing, or utilizing a lower dosage should also be investigated.

5. Conclusions

In this study, the pharmacokinetics of gabapentin in goats were investigated after SD and MD administration at 15 mg/kg. Plasma concentrations appear similar to those described for calves, although elimination and time to maximum concentration appear to be shorter. MD administration revealed accumulation that extended elimination half‐life and maximum plasma concentrations. Clinicians should be aware of the potential for increased accumulation ratio with the administration of multiple doses, and future directions could evaluate the co‐administration of gabapentin with NSAIDs as well as establish effective target concentrations for goats.

Author Contributions

J.C.Z. and M.H. contributed to the method design and coordinated study execution. Analysis of plasma samples was performed by S.C. and J.S.S. coordinated the data and performed pharmacokinetic analysis. All authors contributed to the writing of the manuscript and have approved the final manuscript.

Ethics Statement

The authors' confirm that approval from the Institutional Animal Care and Use Committee was acquired prior to commencement of this study (University of California Davis IACUC protocol # 22828). Additionally, the animals were treated in a humane and ethical way and all study details comply with the Journal's ethical policies.

Conflicts of Interest

The authors' have no conflicts of interest to declare. The authors declare extralabel drug use of gabapentin in goats, which is allowable in the United States with a valid Veterinarian Client Patient Relationship as described by AMDUCA.

Acknowledgements

This study was conducted with funding from UC Davis Center for Companion Animal Health. We would like to acknowledge the excellent technical assistance from Sarah Blasczynski and Dr. Fauna Smith. We would also like to acknowledge UC Davis Animal Science Goat Teaching and Research Facility and Benjamin Rupchis for providing animal care and the healthy goats needed for this study.

Funding: This work was supported by UC Davis Center for Companion Animal Health 2021 Faculty Research Call.

Data Availability Statement

Data is available from the authors upon reasonable request.

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Associated Data

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

Data Availability Statement

Data is available from the authors upon reasonable request.

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