Minzi Omary Mashiku, Mnkugwe Rajabu Hussein, Ngaimisi Eliford, Kinung'hi Safari, Hansson Anna, Pohanka Anton, Kamuhabwa Appolinary, Aklillu Eleni
Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, 11103 Dar es Salaam, Tanzania.
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
Pharmaceuticals (Basel). 2021 Apr 23;14(5):400. doi: 10.3390/ph14050400.
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 infected children treated with PZQ alone ( = 32) or PZQ + DHP combination ( = 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 AUC 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 AUC 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 C 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 C 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 C 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.
吡喹酮（PZQ）和双氢青蒿素 - 哌喹（DHP）联合用药最近显示出比单独使用PZQ治疗肠道血吸虫病更有效的效果。在这项随访研究中，我们调查了在64名受感染儿童中，DHP联合用药对PZQ及其对映体药代动力学的影响，这些儿童分别单独接受PZQ治疗（n = 32）或接受PZQ + DHP联合治疗（n = 32）。给药后0、1、2、4、6和8小时采集的血浆样本使用超高效液相色谱 - 串联质谱法（UPLCMS/MS）进行定量。接受PZQ + DHP治疗的儿童中，总PZQ、R - PZQ和S - PZQ的AUC几何均值（GM）显著高于单独接受PZQ治疗的儿童。PZQ + DHP与PZQ相比，总PZQ、R - PZQ和S - PZQ的AUC几何均值比（GMR）及（90%置信区间）分别为2.18（1.27，3.76）、3.98（2.27，7.0）和1.86（1.06，3.28）。总PZQ、R - PZQ和S - PZQ的AUC的GMR及（90%置信区间）分别为1.73（1.12，2.69）、2.94（1.75，4.92）和1.50（0.97，2.31）。接受PZQ + DHP治疗的儿童中，总PZQ、R - PZQ和S - PZQ的Cmax几何均值显著高于单独接受PZQ治疗的儿童。PZQ + DHP与PZQ相比，总PZQ、R - PZQ和S - PZQ的Cmax的GMR（90%置信区间）分别为1.75（1.15，2.65）、3.08（1.91，4.96）和1.50（1.0，2.25）。总PZQ、R - PZQ和S - PZQ的AUC和Cmax的GMR的90%置信区间均超出了可接受的0.80 - 1.25范围，表明两个治疗组生物不等效。DHP联合用药显著增加了PZQ的全身暴露，这可能有助于PZQ + DHP联合疗法比单独使用PZQ治疗血吸虫病更有效。
