Table 1.
Representative parameter estimates in various populations
| Dosage regimen |
Patient population |
PK model | No. of pts | Cmax (mg/L) |
MRT (h) | AUC (mg.h/L) |
VSS (L) | V (L/kg) | V1 (L) | t1/2 (h) | CL (mL/ min) |
CL (L/h) | CL (mL/ min/kg) |
References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 500 mg Single | Healthy adults | NA | 9 | 39.1 ± 3.5 | NA | 70.8 ± 6.7 | 18 ± 2 | NA | NA | 2 ± 0.3 | 120 ± 8 | 7.2 ± 0.48 | NA | Maxipime prescribing information 2021 |
| 1 g Single | Healthy adults | NA | 9 | 81.7 ± 5.1 | NA | 148.5 ± 15.1 | 18 ± 2 | NA | NA | 2 ± 0.3 | 120 ± 8 | 7.2 ± 0.48 | NA | Maxipime prescribing information 2021 |
| 2 g Single | Healthy adults | NA | 9 | 163.9 ± 25.3 | NA | 284.8 ± 30.6 | 18 ± 2 | NA | NA | 2 ± 0.3 | 120 ± 8 | 7.2 ± 0.48 | NA | Maxipime prescribing information 2021 |
| 1 g Single, infused over 30 min | CrCL >90 mL/min | Non-compartmental | 5 | 63.5 ± 7.79 | 2.86 ± 0.24 | 131 ± 22.8 | 20.5 ± 4.84 | NA | NA | 2.29 ± 0.55 | 131.0 ± 24.6 | 7.86 ± 1.476 | NA | Barbhaiya et al. (1990) [21] |
| 1 g Single, infused over 30 min | CrCL 61-90 mL/min | Non-compartmental | 5 | 70.5 ± 20.8 | 4.60 ± 0.58 | 225 ± 37.7 | 19.6 ± 2.99 | NA | NA | 3.33 ± 0.74 | 75.7 ± 12.9 | 4.542 ± 0.774 | NA | |
| 1 g Single, infused over 30 min | CrCL 31-60 mL/min | Non-compartmental | 5 | 73.9 ± 19.5 | 5.88 ± 1.16 | 292 ± 89.3 | 19.8 ± 3.05 | NA | NA | 4.89 ± 0.82 | 61.0 ± 16.6 | 3.66 ± 0.996 | NA | |
| 1 g Single, infused over 30 min | CrCL 11–30 mL/min | Non-compartmental | 5 | 68.9 ± 16.0 | 14.7 ± 3.39 | 683 ± 192 | 21.8 ± 5.10 | NA | NA | 10.5 ± 2.96 | 25.9 ± 6.73 | 1.554 ± 0.4038 | NA | |
| 1 g Single, infused over 30 min | CrCL < 10 mL/min, hemodialysis maintenance | Non-compartmental | 5 | 65.5 ± 9.18 | 20.0 ± 3.84 | 928 ± 202 | 21.7 ± 4.20 | NA | NA | 13.5 ± 2.65 | 18.7 ± 5.18 | 1.122 ± 0.3108 | NA | |
| 1 g Single, infused over 5 min | GFR 107 ± 4.1 mL/[min × 1.73 m2], healthy adults | Non-compartmental | 5 | 109.2 ± 22.6c | 2.39 ± 0.09 | 153 ± 30c | 0.21 ± 0.03 | NA | NA | 1.8 | NA | NA | 97.2 ± 7.8 (ml/[min × 1.73 m2]) | Cronqvist et al. (1992) [22] |
| 1 g Single, infused over 5 min | GFR 42.5 ± 9.9 mL/[min × 1.73 m2] | Non-compartmental | 6 | 114.9 ± 15.3 | 6.75 ± 1.56 | 482 ± 142 | NA | 0.20 ± 0.03 | NA | 4.7 | NA | NA | 34.6 ± 9.6 (ml/[min × 1.73 m2]) | |
| 1 g single, infused over 5 min | GFR 22.0 ± 5.8 mL/[min × 1.73 m2] | Non-compartmental | 7 | 117.7 ± 21.6 | 11.43 ± 3.68 | 897 ± 257 | NA | 0.20 ± 0.02 | NA | 7.55 | NA | NA | 19.8 ± 6.3 (ml/[min × 1.73 m2]) | |
| 1 g Single, infused over 5 min | End-stage renal disease, hemodialysis | Non-compartmental | 3 | 130.4 ± 23.4 | 31.56 ± 6.11 | 2,659 ± 361 | NA | 0.18 ± 0.06 | NA | 21.13 | NA | NA | 6.3 ± 2.3 (ml/[min × 1.73 m2]) | |
| 1g q12h | Respiratory tract infection | Multi-compartmental | 10 | 71.2 ± 17.2 | 3.57 ± 0.73 | 251 ± 97.5 | NA | NA | NA | 3.92 ± 1.28 | NA | NA | 73 ± 19.7 (ml/[min × 1.73 m2]) | Kovarik et al. (1990) [73] |
| 50 mg/kg q8h | Cystic fibrosis | Non-compartmental | 12 | 141.3 ± 34.9 | 2.28 ± 1.00 | 277 ± 103 | NA | 0.39 ± 0.14 L/ kg |
NA | 1.73 ± 0.69 | NA | NA | 3.09 ± 1.05 | Arguedas et al. (1992) [23] |
| 2g q12h | Acute cholecystitis | NA | 15 | 122.1 ± 28.5 | 2.4 ± 0.4 | 216.1 ± 62.7 | NA | 0.26 ± 0.07 L/kg | NA | 1.79 ± 0.38 | 167.9 ± 0.38 | 10.074 ± 0.0228 | NA | Okamotol et al. (1993) [71] |
| 2g q12h, Infused over 30 min | Nosocomial pneumonia | Non-compartmental | 11 | 97 ± 8 | 5.3 ± 5.9 | 226 ± 107 | 0.413 ± 0.118 L/Kg | 0.513 ± 0.180 L/Kg | NA | 4.33 ± 4.32 | NA | NA | 2.18 ± 1.4 | Chapuis et al. (2010) [25] |
| 2 g q8 h, Infused over 3 h | Ventilator-associated pneumonia | Two compartment | 26 | NA | NA | NA | NA | 0.263 ± 0.187 L/kg | 22.1 ± 6.1 | 7.37 ± 11.55a | NA | 7.6 ± 3.3 | 126.7 ± 55 | Nicasio et al. (2009) [26] |
| 2g q8h | Febrile neutropenia | Non-compartmental | 12 | NA | NA | 269 | 33.4 | NA | NA | 2.7 | NA | 8.6 | NA | Sime et al. (2015) [33] |
| 2g q8h | Febrile neutropenia | One compartment | 9 | NA | NA | NA | 20.9 ± 1.3 | NA | NA | 1.78 ± 1.7a | NA | 8.15 ± 0.04a | NA | Whited et al. (2016) [34] |
| 2g q8h | Febrile neutropenia | Two compartment | 9 | NA | NA | NA | NA | NA | 14.8 ± 3.8 | 1.62 ± 0.19a | NA | 6.33 ± 1.05 | NA | Rhodes et al. (2017) [31] |
| 2g q8h | Febrile neutropenia | Two compartment | 15 | NA | NA | NA | NA | NA | 26.43 ± 4.01 | 0.80a | NA | 12.88 | NA | Alvarez et al. (2021) [32] |
| 2g Single, infused over 3 min (1 day) | Critically ill septic | Two compartment | 10 | NA | 3.1 ± 1.1 | 283 ± 85 | 21.8 ± 5.1 | NA | NA | 3.0 ± 1.2 | 127 ± 33 | 7.62 ± 1.98 | NA | Lipman et al. (1999) [27] |
| 2g Single, infused over 3 min | Critically ill septic | Non-compartmental (initial dose) | 13 | NA | NA | 339 ± 149 | 23 ± 5 | NA | NA | 3.3 ± 1.5 | 113 ± 40 | 6.78 ± 2.4 | NA | Lipman et al. (2003) [30] |
| 2g q12h, Infused over 3 min | Critically ill septic | Non-compartmental (subsequent dose) | 12 | NA | NA | 346 ± 225 | 24 ± 8 | NA | NA | 3.2 ± 2.1 | 127 ± 42 | 7.62 ± 2.52 | NA | |
| 2g q12h, Infused over 3 min | Critically ill septic | Three compartment | 13 | NA | NA | NA | NA | NA | 5.74 | NA | NA | 6.51 | NA | Roos et al. (2006) [28] |
| 2g q12h, Infused over 30 min | Sepsis syndrome | Non-compartmental | 7 | 94.2 ± 23.9 | 4.4 ± 1.2 | 305 ± 115 | 32.6 ± 17.5 | NA | NA | 3.42 ± 1.12 | 125 ± 51 | 7.5 ± 3.06 | NA | Kieft et al. (1993) [37] |
| NA | Adult and pediatric | Two compartment | 33 | NA | NA | NA | 11.172 (median) | NA | 1.716 (median) | 2.936 (median) | NA | 2.63 (median) | NA | Liu et al. (2020) [38] |
| NA | Septic patients with ARC | One compartment | 11 | 40.7 (35.4–48.3) median (IQR) | NA | NA | 47.8 | NA | NA | 2.5 (2.0-3.0) median (IQR) | NA | 18.8 | NA | Jacobs et al. (2018) [39] |
| 2g q8h, Infused over 20 min | Burn patients | NA | 13 | 140.4 ± 58.7 | NA | 840 | NA | 0.31 ± 0.13 | NA | 2.9 ± 3.2 | 119.1 ± 59.6 | 7.146 ± 3.57 | NA | Conil et al. (2007) [76] |
| 2g single, Infused over 30 min | Sepsis patients | One compartment | 19 | 68 (51-86) median (range) | NA | 310 (234-422) median (range) | NA | 0.36 (0.33–0.44) median (range) | NA | 3.37 (2.26-5.34) median (range) | NA | 5.292 (4.494-8.19) median (range) | 1.26 (1.07-1.95) median (range) | Taccone et al. (2010) [110] |
| 1.3-1.8g target controlled infustion, 4days | Critically ill | Two compartment | 21 | NA | NA | NA | NA | NA | 10.7 | NA | NA | NA | NA | Jonchkeere et al. (2019) [111] |
| 4 g/d, Continuous infusion | Critically ill | NA | 26 | NA | NA | 612 ± 369 | NA | NA | NA | NA | NA | NA | NA | Georges et al. (2005) [4] |
| 2g q12h, Infused over 30 min | Critically ill | NA | 24 | 115 | NA | 623 ± 319 | NA | NA | NA | NA | NA | NA | NA | |
| NA | Pediatric, ECMO | Two compartment | 17 | NA | NA | NA | NA | NA | 1.17/5.8 kg | NA | 7.1/5.8kg | 0.426/5.8 kg | 1.22 | Zuppa et al. (2019) [59] |
| 4g/d, 76.6 mg/min Intermittent infusion | Adult, ECMO | Two compartment | 5 | NA | NA | NA | 15.09 ± 3.33 | NA | NA | 4.3 ± 1.49 | NA | 2.43 ± 1.55 | NA | Cheng et al. (2021) [60] |
| 2g q8h, By continuous venovenous hemodiafiltration | Adult, ECMO | Two compartment | 1 | NA | NA | NA | 16.63 | NA | NA | NA | NA | 1.04 | NA | |
| 1g Single, infused over 30 min | Hemodialysis | NA | 5 | NA | NA | NA | NA | NA | NA | NA | 60.1 ± 2.6 for 100 mL/min dialysis blood flow rate | 3.606 ± 0.156 for 100 mL/min dialysis blood flow rate | NA | Maynor et al. (2008) [61] |
| 2g 3x/wk Post-dialysis | Hemodialysis | Non-compartmental | 6–intradialytic | 78.6 ± 10.2 | NA | 178.2 ± 32.2 | NA | NA | 16.7 ± 5.6 | 1.6 ± 0.29 | 126.8 ± 24.0 | 7.608 ± 1.44 | NA | Schmaldienst et al. (2000) [62] |
| Non-compartmental | interdialytic | 93.6 ± 40.1 | NA | 2327.3 ± 288.9 | NA | NA | NA | 22 ± 2.14 | 14.5 ± 1.7 | 0.87 ± 0.102 | NA | |||
| ~ 1g 3x/wk Post-dialysis as a 5-10 min infusion | Hemodialysis | NA | 9 | 10.7 ± 3.9 (pre-dialysis) | NA | NA | NA | NA | NA | NA | NA | NA | NA | Descombes et al. (2016) [63] |
| 1.96 ± 1.2 (post-dialysis) | NA | NA | NA | NA | NA | NA | NA | NA | NA | |||||
| 2g q8h, Infused over 30 min | CRRT | One compartment | 3 | 74.5 (52.0–75.0) | NA | NA | 19.4 (15.8-23.1) median (range) | 0.26 (0.24–0.28) median (range) | NA | 4.3 (1.5-9.7) median (range) | NA | 0.0524 (0.0273–0.1209) | NA | Beumier et al. (2014) [66] |
| 6 | 93.4 (50.5–165.0) | NA | NA | 19.2 (11.4–32.9) median (range) | 0.21 (0.16–0.51) median (range) | NA | 8.0 (6.0-35.3) median (range) | NA | 0.023 (0.005–0.058) median (range) | NA | ||||
| 2g q8h, Infused over 4h, extended or continuous infusion | CRRT | Five compartment | 10 | NA | NA | NA | 26.76 ± 15.09 | NA | NA | 9.9 ± 13.89 | NA | 1.87 ± 0.753 | NA | Al-Shaer et al. (2021) [44] |
| 2g q8h or 2g q12h, Infused over 30 min | CRRT | One compartment | 13 | NA | NA | NA | 40.9 | NA | NA | NA | NA | 4.4 | NA | Carlier et al. (2015) [67] |
| 2g Loading dose followed by 1g q6h | Extended or continuous infusion | One compartment | 5000 | NA | NA | NA | NA | 0.48 ± 0.24 | NA | NA | 24.33 ± 11.25 (non-renal) | 1.46 ± 0.675 | NA | Jang et al. (2018) [69] |
| 1 g Single, infused over 30 min | Peritoneal dialysis | Non-compartmental | 5 | 62.9 ± 15.8 | 24.0 ± 3.1 | 1166 ± 356 | 21.7 ± 4.8 | NA | NA | 17.6 ± 2.9 | 15.4 ± 4.9 | 0.924 ± 0.294 | NA | Barbhaiya et al. (1992) [64] |
| 2 g Single, infused over 30 min | Adult, non-infected, continuous ambulatory peritoneal dialysis | Non-compartmental | 5 | 124 ± 14 | 26.8 ± 1.5 | 2405 ± 213 | 22.5 ± 2.8 | NA | NA | 18.8 ± 1.6 | 14.0 ± 1.3 | 0.84 ± 0.078 | NA | |
| 15 mg/kg ip | Adult, non-infected, automated peritoneal dialysis | Mono-exponential model | 6 | 38.5 ± 5.1 | NA | NA | NA | 0.34 ± 0.07 | NA | 13.8 ± 3.2 | 16.5 ± 4.4 | 0.99 ± 0.264 | NA | Elwell et al. (2005) [65] |
| 50 mg/kg q8 h | Children | Non-compartmental | 31 | 184.2 ± 38 | NA | NA | NA | 0.33 ± 0.1 | NA | 1.8 ± 0.6 | NA | NA | 2.8 ± 1.4 | Reed et al. (1997) [82] |
| 50 mg/kg q12 h | Neonates | One compartment | 55 | 89 ± 27b | NA | NA | NA | 0.43 ± 0.13 | NA | 4.9 ± 2.1 | NA | NA | 1.15 ± 0.45 | Cappareli et al. (2005) [79] |
| 50 mg/kg q12 h | Neonates | One compartment | 31 | 120.9 ± 38.5 | NA | NA | NA | 0.41 ± 0.12 | NA | 4.32 ± 1.8 | NA | NA | 1.20 ± 0.49 | Lima-Rogel et al. (2008) [80] |
| 30 mg/kg q12 h | Neonates | One compartment | 85 | NA | NA | 112 to 379 | NA | 0.62 ± 0.24 | NA | 2.387 ± 3.02 | NA | NA | 3.0 ± 0.83 | Zhao et al. (2020) [81] |
Values are expressed as mean ± SD.
NA not available
a
calculated
b
Estimated for a 30 mg/kg every 12 h dose .
c
Two subjects were excluded after being given half the intended dose by mistake.
ECMO, extracorporeal membrane oxygenation; ARC, augmented renal clearance; CRRT, continuous renal replacement therapy Clearance in bold is taken from the reference. Clearance in plain type is converted into the corresponding units.