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.
