Effects of Plasmodium berghei infection on arteether metabolism and disposition.
Pharmacology
; 54(5): 276-84, 1997 May.
Article
en En
| MEDLINE
| ID: mdl-9380774
ABSTRACT
Arteether (AE) is primarily deethylated to dihydroqinghaosu (DQHS) in rats and humans. Conversion of AE to DQHS was impaired in microsomes from rats infected with Plasmodium berghei. The Km for AE was 175.1 +/- 49.1 and 124.4 +/- 115.1 mumol/l, and Vmax was 2.24 +/- 0.45 and 1.22 +/- 0.67 nmol AE formed/mg protein/min in control and infected microsomes (p < 0.05), respectively. Calculated intrinsic clearance (CLint = initial Vmax/Km) for AE was only 4% lower in infected microsomes. Apparent pharmacokinetic parameter estimates for AE using the isolated perfused rat liver demonstrated no differences (p > 0.05) in volume of distribution, clearance, and half-life between normal and infected animals. Malaria infection resulted in decreased biliary excretion of free AE and DQHS. The majority of AE is eliminated via biliary excretion of conjugated DQHS, which is approximately 500-fold higher than free DQHS and 75-fold higher than free AE on a molar basis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plasmodium berghei
/
Sesquiterpenos
/
Artemisininas
/
Malaria
/
Antimaláricos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharmacology
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos