Optimal antimalarial dose regimens for chloroquine in pregnancy based on population pharmacokinetic modelling

Salman, S; Baiwog, F; Page-Sharp, M; Kose, K; Karunajeewa, HA; Mueller, I; Rogerson, SJ; Siba, PM; Ilett, KF; Davis, TME

Author(s): Salman, S; Baiwog, F; Page-Sharp, M; Kose, K; Karunajeewa, HA; Mueller, I; Rogerson, SJ; Siba, PM; Ilett, KF; Davis, TME;
Details: Publication Year 2017-10,Volume 50,Issue #4,Page 542-551
Journal Title: International Journal of Antimicrobial Agents
Publication Type: Journal Article
Abstract: Despite extensive use and accumulated evidence of safety, there have been few pharmacokinetic studies from which appropriate chloroquine (CQ) dose regimens could be developed specifically for pregnant women. Such optimized CQ-based regimens, used as treatment for acute malaria or as intermittent preventive treatment in pregnancy (IPTp), may have a valuable role if parasite CQ sensitivity returns following reduced drug pressure. In this study, population pharmacokinetic-pharmacodynamic modelling was used to simultaneously analyze plasma concentration-time data for CQ and its active metabolite desethylchloroquine (DCQ) in 44 non-pregnant and 45 pregnant Papua New Guinean women treated with CQ and sulfadoxine-pyrimethamine (SP) or azithromycin (AZI). Pregnancy was associated with 16% and 49% increases in CQ and DCQ clearance, respectively, as well as a 24% reduction in CQ relative bioavailability. Clearance of DCQ was 22% lower in those who received AZI in both groups. Simulations based on the final multi-compartmental model demonstrated that a 33% CQ dose increase may be suitable for acute treatment for malaria in pregnancy as it resulted in equivalent exposure to that in non-pregnant women receiving recommended doses, while a double dose would likely be required for an effective duration of post-treatment prophylaxis when used as IPTp especially in areas of CQ resistance. The impact of co-administered AZI was clinically insignificant in simulations. The results of past/ongoing trials employing recommended adults doses of CQ-based regimens in pregnant women should be interpreted in the light of these findings, and consideration given to using increased doses in future trials.
Publisher: Elsevier
Research Division(s): Population Health And Immunity
PubMed ID: 28669839
Publisher's Version: https://doi.org/10.1016/j.ijantimicag.2017.05.011
NHMRC Grants: NHMRC/458555,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-07-26 12:48:14

Last Modified: 2018-05-04 12:01:40