Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity.
Author(s): Lima RM, Ferreira MA, de Jesus Ponte Carvalho TM, Dumet Fernandes BJ, Takayanagui OM, Garcia HH, Coelho EB, Lanchote VL
Affiliation(s): Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Brazil.
Publication date & source: 2011-04, Br J Clin Pharmacol., 71(4):528-35.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
AIM: This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS: A randomized crossover study was carried out in three phases (n= 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0-48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P </= 0.05. RESULTS: The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 microg ml(-1) h), (-)-ASOX by 358% (0.14 vs. 0.50 microg ml(-1) h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 microg ml(-1) h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (-)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (-)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 microg ml(-1) h). CONCLUSIONS: The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (-)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination. (c) 2011 The Authors. British Journal of Clinical Pharmacology (c) 2011 The British Pharmacological Society.