Table 2.
Pentavalent antimonials: primary and secondary pharmacokinetic parameters
| Study | Patients | Weight (kg) | Daily dose | Sampling day | C max (µg/mL) | C trough (µg/mL) | t max (h) | k a (h−1) | V d/F (L) | CL/F (L/h) | AUC (mg·h/L) | t ½ (h) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Non-compartmental | ||||||||||||
| Cruz et al. [11]a | Cutaneous leishmaniasis patients: | |||||||||||
| Adults: 20 mg/kg/day | 62 (56–120) | 20 mg/kg, 20 days | Day 19 | 38.8 ± 2.1 | 0.198 ± 0.023 | 1.0 (1.0–2.0) | NA | 0.30 ± 0.01b,c | 0.106 ± 0.006b | AUC24: 190 ± 10 |
t
½,β: 1.99 ± 0.08 t ½,24–48 h: 20.6 ± 1.8 |
|
| Children: 20 mg/kg/day | 15 (13–18) | 20 mg/kg, 20 days | Day 19 | 32.7 ± 0.9 | 0.113 ± 0.015 | 0.875 (0.5–1.5) | NA | 0.39 ± 0.03b,c | 0.185 ± 0.013b | AUC24: 111 ± 7 | t ½,β: 1.48 ± 0.02 | |
| Children: 30 mg/kg/day | 17.5 (13–21) | 20 mg/kg, 19 days 30 mg/kg, Day 20 |
Day 20 | 43.8 ± 2.3 | 0.102 ± 0.011 | 1.0 (1.0–1.5) | NA | 0.39 ± 0.02b,c | 0.186 ± 0.012b | AUC24: 164 ± 10 |
t
½,β: 1.47 ± 0.06 t ½,24–48 h: 25.3 ± 3.1 |
|
| Zaghloul et al. [19]a | Cutaneous leishmaniasis patients | 66.4 ± 8.7 | First dose 300 mg (~5 mg/kg) | Day 1 | 6.4 ± 1.4d | NA | NA | 3.3e | 239 ± 32.6f | 13.2 ± 1.5 | AUC∞: 49.88 ± 4.43d |
t
½,α: 0.41 ± 0.15 g
t ½,β: 9.4 ± 1.9 g |
| 600 mg (~10 mg/kg), at least 3 weeks | NA | 7.23 ± 1.58 | NA | 1.7 ± 0.19 | 1.9e | 258 ± 44.4f | 12.86 ± 1.58 | AUC∞: 65.4 ± 8.3 |
t
½,α: 1.68 ± 1.3 g
t ½,β: 9.69 ± 2.3 g |
|||
| Compartmental | ||||||||||||
| Al-Jaser et al. [30]a | Cutaneous leishmaniasis patients | 60–75 | 8–10 mg/kg, 10 days | NA | 8.77 ± 0.39 | NA | 1.34 ± 0.09 | 1.71±0.15 | 45.7 ± 2.6 | 17.67 ± 1.38 | 37.0 ± 1.57 |
t
½,α: 0.48 ± 0.035 t ½,β: 1.85 ± 0.072 |
| Chulay et al. [18] | Visceral leishmaniasis patients | 47.4 ± 8.05 | 10 mg/kg, 30 days | Day 1 | 10.5 ± 1.2 | 0.062 ± 0.018 | 2 | 0.8e | 0.22 ± 0.057b | NA | NA |
t
½,β: 2.02 ± 0.25 t ½,γ: 76 ± 28 |
| Pamplin et al. [29]a | Cutaneous leishmaniasis patients | NA | 10 mg/kg, 10 days | NA | NA | NA | NA | 1.76 | NA | NA | NA |
t
½,α: 0.34 ± 0.9 t ½,β: 1.72 ± 0.6 t ½,γ: 32.8 ± 3.8 |
Data given as either mean ± standard deviation or median (range), unless indicated otherwise
AUC area under the concentration–time curve, AUC 24 AUC from time zero to 24 h, AUC ∞ AUC from time zero to infinity, CL clearance, C max peak plasma concentration, C trough trough plasma concentration 24 h after dose, F bioavailability, k a absorption rate constant, NA not available, t ½ plasma elimination half-life, t½,α distribution half-life, t½,β elimination half-life, t½,γ terminal elimination half-life, t½ 24-48h apparent half-life between 24 and 48 h (an approximation of the γ-elimination half-life) t max time to C max, V d volume of distribution
aValues reported as mean ± standard error of the mean
bPer kg
c V β apparent volume of distribution during the β-elimination phase
dData normalized to a 600 mg dose
eDocumented as absorption t ½
f V d is reported as V ss, the steady-state volume of distribution including both the central and peripheral compartment
gCalculated with compartmental analysis, reported as distribution half-life (indicated as t ½,α) and elimination half-life (indicated as t ½,β)