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Repetitive dosing of artemisinin and quinine against Plasmodium falciparum in vitro: a simulation of the in vivo pharmacokinetics.

Abstract：

:Plasmodium falciparum (F32) parasites were exposed to artemisinin and quinine for 3 and 4 h, respectively, once or twice daily and for 3, 5 or 7 days. Between the peaks the parasites were exposed to trough concentrations. Continuous drug exposure was also assessed for comparison. After drug exposure, the cultures were extended for an observation period of up to 30 days to assess the viability of the parasites remaining after drug exposure. For artemisinin, a critical threshold concentration of 3 x 10(-8) M was required for growth inhibition. Dosing twice daily for at least 5 days was also critical. Prolonging the duration of drug exposure to 7 days further increased the efficacy. For quinine the results were quite different. The concentration dependency of the efficacy was more gradual. On the other hand dosing once daily appeared to be nearly as effective as twice daily and radical clearance was obtained even after 3 days of exposure at peak concentrations of 10(-5) M. A concentration of 10(-6) M provided the same effect if the duration was extended to 7 days. There was a strong similarity between estimated concentrations of free unbound drug required for radical clearance in vitro and those empirically required for clinical efficacy in vivo. This suggests that the in vitro model represents an appropriate model for estimating drug efficacy and pharmacodynamics if the in vitro system is adapted to simulate in vivo pharmacokinetics.

journal_name

Acta Trop

journal_title

Acta tropica

authors

Bwijo B,Hassan Alin M,Abbas N,Eriksson O,Björkman A

doi

10.1016/s0001-706x(96)00565-7

subject

Has Abstract

pub_date

1997-04-30 00:00:00

pages

11-22

issue

1

eissn

0001-706X

issn

1873-6254

pii

S0001706X96005657

journal_volume

65

pub_type

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