title: Pharmacokinetic interactions between topiramate and diltiazem, hydrochlorothiazide, or propranolol.
abstract: Drug-drug interactions between topiramate and diltiazem, hydrochlorothiazide, or propranolol were evaluated along with safety/tolerability in three open-label studies. Healthy participants (aged 18-45 years) received topiramate 75 mg every 12 hours (q12h) and diltiazem 240 mg/day (study 1); topiramate 96 mg q12h and hydrochlorothiazide 25 mg/day (study 2); topiramate 100 mg q12h and propranolol 40-80 mg q12h (study 3). The pharmacokinetic parameters for topiramate, diltiazem (and active metabolites, desacetyldiltiazem [DEA], N-demethyl diltiazem [DEM]), hydrochlorothiazide, and propranolol (and its active metabolite) were assessed at steady state. Results showed no effect of diltiazem on topiramate pharmacokinetics. However, a modest reduction in systemic exposures of diltiazem and DEA (10-27%) occurred during coadministration with topiramate. Systemic exposure of DEM was unaffected. Furthermore, oral and renal clearance of topiramate decreased (22-30%) significantly (P < 0.05) during coadministration with hydrochlorothiazide, while systemic exposure increased by 27-29%. Topiramate had no effect on hydrochlorothiazide pharmacokinetics. The results demonstrated lack of pharmacokinetic interaction between topiramate and propranolol. Overall, no new safety concerns emerged when topiramate was coadministered with diltiazem, hydrochlorothiazide, or propranolol.
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Prasarn
authors.initials: P
authors.lastname: Manitpisitkul
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Curtin
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Shalayda
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Shean-Sheng
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ford
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Heald
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001711:Biotransformation; D004110:Diltiazem / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077236:Topiramate; D014481:United States; D055815:Young Adult
chemical_list: D000077236:Topiramate; D006852:Hydrochlorothiazide; D005632:Fructose; D011433:Propranolol; D004110:Diltiazem
keywords: diltiazem; drug-drug interactions; hydrochlorothiazide; pharmacokinetics; propranolol; topiramate