Abstract
ABSTRACTAntimalarial drugs have usually been first deployed in areas of malaria endemicity at doses which were too low, particularly for high-risk groups such as young children and pregnant women. This may accelerate the emergence and spread of resistance, thereby shortening the useful life of the drug, but it is an inevitable consequence of the current imprecise method of dose finding. An alternative approach to dose finding is suggested in which phase 2 studies concentrate initially on pharmacokinetic-pharmacodynamic (PK-PD) characterization andin vivocalibration ofin vitrosusceptibility information. PD assessment is facilitated in malaria because serial parasite densities are readily assessed by microscopy, and at low densities by quantitative PCR, so that initial therapeutic responses can be quantitated accurately. If thein vivoMIC could be characterized early in phase 2 studies, it would provide a sound basis for the choice of dose in all target populations in subsequent combination treatments. Population PK assessments in phase 2b and phase 3 studies which characterize PK differences between different age groups, clinical disease states, and human populations can then be combined with the PK-PD observations to provide a sound evidence base for dose recommendations in different target groups.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
82 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献