AIM: This study intends to assess the pharmacokinetic properties and treatment response of lumefantrine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria infection in Western Kenya. METHODS: Seventy-five women with uncomplicated P. falciparum malaria were enrolled, including 25 non-pregnant, 30 pregnant women in the second trimester and 20 pregnant women in their third trimester. The participants received a standard dose of artemether-lumefantrine (80/480 mg) twice daily for 3 days. Densely venous plasma samples were collected. Nonlinear mixed-effects modelling was used to characterize the pharmacokinetic properties of lumefantrine, and the effects of pregnancy was assessed on all pharmacokinetic parameters by a full covariate modelling approach. RESULTS: The concentration-time data of lumefantrine were described adequately by a two-compartment disposition model, with a flexible transit absorption and first-order elimination. Covariate modelling results demonstrated that pregnancy status or gestational age had a significant impact on both elimination clearance (CL) and the central volume of distribution (Vc) of lumefantrine. The estimated pregnancy effects on CL and Vc were 23% (95%CI: 10.8-34.8%) and 28% (95%CI: 7.3-51.8%), respectively. Pregnant women exhibited lower drug exposure compared to non-pregnant women, with the geometric mean ratios (GMRs) of 0.76 (95% CI: 0.57-1.01), 0.79 (95% CI: 0.63-0.99) and 0.69 (95% CI: 0.51-0.94) for area under the concentration-time curve (AUC), maxinum concentration (Cmax) and Day 7 concentration, respectively. Other covariates did not significantly affect the pharmacokinetics of lumefantrine. The 28-day polymerase chain reaction (PCR)-corrected parasitological cure was 100% for both pregnant and non-pregnant women. CONCLUSIONS: The exposure to lumefantrine was lower in pregnant women, compared to non-pregnant women, with uncomplicated P. falciparum infection. This lower drug exposure might increase the risk of treatment failure with artemether-lumefantrine in pregnant women, especially if susceptibility to either drug is reduced. Continuous assessment and monitoring of the efficacy of artemether-lumefantrine in pregnant women are warranted.