Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.
J Vet Pharmacol Ther
; 40(6): 675-681, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-28455999
The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.15 (0.13-0.18) L hr-1 kg-1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (Cmax ; median: 0.72, range: 0.55-0.93 µg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triazoles
/
Phascolarctidae
/
Antifúngicos
Límite:
Animals
Idioma:
En
Revista:
J Vet Pharmacol Ther
Año:
2017
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Reino Unido