Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The antiparasitic drugs albendazole and prazoquantel have been used together before for geohelminths, echinococcosis and cysticercosis, but there is only scarce and discrepant data on the pharmacokinetics of these drugs when given together. WHAT THIS STUDY ADDS • This is a randomized, double‐blinded, placebo‐controlled phase II evaluation of the pharmacokinetics of albendazole and praziquantel in 32 patients with neurocysticercosis which demonstrates that combined albendazole + praziquantel is associated with increased albendazole sulfoxide concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double‐blind, placebo‐controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty‐one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.