scholarly journals Population Pharmacokinetics and Pharmacodynamics of Piperaquine in Children With Uncomplicated Falciparum Malaria

2012 ◽  
Vol 91 (3) ◽  
pp. 497-505 ◽  
Author(s):  
J Tarning ◽  
I Zongo ◽  
F A Somé ◽  
N Rouamba ◽  
S Parikh ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Falciparum Malaria ◽  
Uncomplicated Falciparum Malaria ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Population Pharmacokinetics And Pharmacodynamics

scholarly journals Population Pharmacokinetics and Pharmacodynamics of Artemether and Lumefantrine during Combination Treatment in Children with Uncomplicated Falciparum Malaria in Tanzania

2010 ◽  
Vol 54 (11) ◽  
pp. 4780-4788 ◽  
Author(s):  
Sofia Friberg Hietala ◽  
Andreas Mårtensson ◽  
Billy Ngasala ◽  
Sabina Dahlström ◽  
Niklas Lindegårdh ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Falciparum Malaria ◽  
Compartment Model ◽  
Uncomplicated Falciparum Malaria ◽  
Oral Clearance ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Population Pharmacokinetics And Pharmacodynamics ◽  
Drug Concentrations ◽  
Rough Approximation ◽  
Parasite Dynamics

ABSTRACT The combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were included in the model of the parasite dynamics. The population pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine were modeled in NONMEM. The distribution of artemether was described by a two-compartment model with a rapid absorption and elimination through metabolism to dihydroartemisinin. Dihydroartemisinin concentrations were adequately illustrated by a one-compartment model. The pharmacokinetics of artemether was time dependent, with typical oral clearance increasing from 2.6 liters/h/kg on day 1 to 10 liters/h/kg on day 3. The pharmacokinetics of lumefantrine was sufficiently described by a one-compartment model with an absorption lag time. The typical value of oral clearance was estimated to 77 ml/h/kg. The proposed semimechanistic model of parasite dynamics, while a rough approximation of the complex interplay between malaria parasite and the human host, adequately described the early effect of ARM and DHA concentrations on the parasite density in malaria patients. However, the poor precision in some parameters illustrates the need for further data to support and refine this model.

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