title: Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Cysticercosis Unit, Department of Transmissible Diseases, Instituto Nacional de Ciencias Neurologicas, Jr. Ancash 1271, Barrios Altos, Lima. hgarcia@jhsph.edu
authors.forename: Hector H
authors.initials: HH
authors.lastname: Garcia
authors.forename: Andres G
authors.initials: AG
authors.lastname: Lescano
authors.forename: Vera L
authors.initials: VL
authors.lastname: Lanchote
authors.forename: E Javier
authors.initials: EJ
authors.lastname: Pretell
authors.forename: Isidro
authors.initials: I
authors.lastname: Gonzales
authors.forename: Javier A
authors.initials: JA
authors.lastname: Bustos
authors.forename: Osvaldo M
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: Pierina S
authors.initials: PS
authors.lastname: Bonato
authors.forename: John
authors.initials: J
authors.lastname: Horton
authors.forename: Herbert
authors.initials: H
authors.lastname: Saavedra
authors.forename: Armando E
authors.initials: AE
authors.lastname: Gonzalez
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
mesh_terms: D000293:Adolescent; D000328:Adult; D015766:Albendazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D020019:Neurocysticercosis / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology; D010568:Peru; D011223:Praziquantel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D041201:Taenia solium / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D011223:Praziquantel; D015766:Albendazole