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. AIMSNeurocysticercosis 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. METHODSA 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. RESULTSTwenty-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. CONCLUSIONSCombined 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.

Current status and future perspectives on the medical treatment of neurocysticercosis

“…Combinations of antiparasitic drugs, namely albendazole with praziquantel, have been anecdotally used, appear safe, and are likely associated with improved parasiticidal efficacy. [34][35][36] A second option reported in the literature is to increase the dose of albendazole up to 30 mg/kg/day, although the small numbers of treated patients do not yet allow conclusions regarding the safety of these regimes. 37,38 After appropriate pre-clinical work, human use of the veterinary drug oxfendazole may provide a more efficacious parasiticidal drug.…”

Neurocysticercosis in a European Traveler Returning From India Primarily Suspected as Neoplasia

“…Recent studies showed that the combination of praziquantel and albendazole increased the albendazole plasma concentration and therefore may improve the clinical outcome. 13 To control treatment-induced inflammation and therefore to reduce the likelihood of seizures we also started dexamethason treatment. [14][15][16] Conclusion NCC should be kept in mind in patients with a travel history to T solium endemic areas suffering from seizures associated with subcutaneous nodules.…”

Unusual cases of Taenia crassiceps cysticercosis in naturally infected animals in the Czech Republic

“…Experiments in mice showed a significant reduction of cysticerci after prolonged 20-and 25-day administration of albendazole (Zurabian et al 2013). In human medicine, the synergistic action of praziquantel and albendazole was employed to successfully treat infection (Garcia et al 2011;Fraga et al 2012;Anikpeh et al 2014). As for regular deworming of dogs, it is not effective against T. crassiceps cysticercosis, but may help to prevent contamination of the environment by tapeworm eggs contained in faeces of dogs parasitised by adult tapeworms in the intestine.…”