Piperaquine exposure is altered by pregnancy, HIV and nutritional status in Ugandan women.

Piperaquine exposure is altered by pregnancy, HIV and nutritional status in Ugandan women. Antimicrob Agents Chemother. 2020 Oct 05;: Authors: Hughes E, Imperial M, Wallender E, Kajubi R, Huang L, Jagannathan P, Zhang N, Kakuru A, Natureeba P, Mwima MW, Muhindo M, Mwebaza N, Clark TD, Opira B, Nakalembe M, Havlir D, Kamya M, Rosenthal PJ, Dorsey G, Aweeka F, Savic RM Abstract Dihydroartemisinin-piperaquine (DHA-PQ) provides highly effective therapy and chemoprevention for malaria in pregnant African women. PQ concentrations >10.3 ng/mL have been associated with reduced maternal parasitemia, placental malaria and improved birth outcomes. We characterized the population pharmacokinetics (PK) of PQ in a post-hoc analysis of human immunodeficiency virus (HIV)-infected and -uninfected pregnant women receiving DHA-PQ as chemoprevention every 4 or 8 weeks. The effects of covariates such as pregnancy, nutritional status (body mass index, BMI) and efavirenz (EFV)-based antiretroviral therapy were investigated. PQ concentrations from two chemoprevention trials were pooled to create a population PK database from 274 women and 2218 PK observations. A three-compartment model with an absorption lag best fit the data. Consistent with our prior intensive PK evaluation, pregnancy and EFV use resulted in a 72% and 61% increased PQ clearance, compared to post-partum and HIV-uninfected pregnant women, respectively. Low BMI at 28-weeks gestation was a...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research