Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection

Abstract

Praziquantel (PZQ) and dihydroartemisinin-piperaquine (DHP) combination recently showed superior effectiveness than PZQ alone to treat intestinal schistosomiasis. In this follow-up study, we investigated the effect of DHP co-administration on the pharmacokinetics of PZQ and its enantiomers among 64 Schistosoma mansoni infected children treated with PZQ alone (n = 32) or PZQ + DHP combination (n = 32). Plasma samples collected at 0, 1, 2, 4, 6, and 8 h post-dose were quantified using UPLCMS/MS. The geometric mean (GM) of AUCs for total PZQ, R-PZQ and S-PZQ were significantly higher among children who received PZQ + DHP than PZQ alone. The geometric mean ratio (GMR) and (90% CI) of AUC0–∞ for PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 2.18 (1.27, 3.76), 3.98 (2.27, 7.0) and 1.86 (1.06, 3.28), respectively. The GMR and (90% CI) of AUC0–8 for total PZQ, R-PZQ, and S-PZQ were 1.73 (1.12, 2.69), 2.94 (1.75, 4.92), and 1.50 (0.97, 2.31), respectively. The GM of Cmax for total PZQ, R-PZQ and S-PZQ were significantly higher among those who received PZQ + DHP than PZQ alone. The GMR (90% CI) of Cmax of PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 1.75 (1.15, 2.65), 3.08 (1.91, 4.96), and 1.50 (1.0, 2.25%), respectively. The 90% CI of the GMRs for both AUCs and Cmax for total PZQ, R-PZQ, and S-PZQ were outside the acceptable 0.80–1.25 range, indicating that the two treatment arms were not bioequivalent. DHP co-administration significantly increases systemic PZQ exposure, and this may contribute to increased effectiveness of PZQ + DHP combination therapy than PZQ alone to treat schistosomiasis.

Efficacy and safety of praziquantel plus Artemisinin-based combinations in the treatment of Kenyan children withSchistosoma mansoniinfection: an open-label, randomized, head-to-head, non-inferiority (SCHISTOACT) trial

“…Our results contrast a recent study in which PZQ + DHAP had superior efficacy to PZQ alone in children with S. mansoni infections at 3- and 8 weeks post-treatment [8]. Adding dihydroartemisinin may have improved the bioavailability of PZQ [22]. However, it is unclear why children who received PZQ+DHAP in our study had an increased risk of reinfection at week 12.…”

Safety of Praziquantel and Albendazole Coadministration for the Control and Elimination of Schistosomiasis and Soil-Transmitted Helminths Among Children in Rwanda: An Active Surveillance Study

“…In most SSA countries, schistosomiasis and STH are coendemic, hence praziquantel and albendazole are coadministered during MDA. Although coadministration of the two drugs targeting the two NTDs is cost effective, several factors, including risk for drug interaction and overlapping toxicities, underscores the need for safety monitoring [ 14 , 15 ]. Safety monitoring is essential to detect the number, type, and severity of AEs and identify risk factors associated with mass albendazole and praziquantel administration-related AEs for timely interventions, thereby minimizing harm and sustaining public confidence in the MDA [ 16 ].…”

Safety and Tolerability of Ivermectin and Albendazole Mass Drug Administration in Lymphatic Filariasis Endemic Communities of Tanzania: A Cohort Event Monitoring Study

“…The safety profile of drugs used in public health programs vary between individuals and populations due to host-genetic and environmental factors, including coinfection, comorbidity, and drug-interactions and the use of traditional medicines, which is common in Africa [ 19 , 20 , 21 , 22 , 23 ]. Poor safety surveillance of medicines during MDA campaigns and the under-reporting rate of AEs in SSA makes it challenging to accurately estimate the risks of drugs used in MDA to inform healthcare policy and practice.…”