title: Pharmacokinetics and hemodynamic effects of nisoldipine and its interaction with cimetidine.
abstract: Pharmacokinetics, diastolic blood pressure, and heart rate after oral and intravenous nisoldipine were studied in eight healthy subjects without and with cotreatment of cimetidine in a four-way crossover design. After intravenous infusion, elimination half-life (t1/2) was 4.0 +/- 2.3 hours, systemic clearance (CL) was 0.83 +/- 0.17 L/min, and volume of distribution was 1.6 +/- 0.6 L/kg. After oral nisoldipine, t1/2 was 3.8 +/- 1.3 hours and systemic availability was 3.9% +/- 3.5%. During cimetidine, t1/2 and CL were not different. Systemic availability increased to 5.7% +/- 2.8%. After all nisoldipine treatments a significant decrease in supine diastolic blood pressure (mean 10% to 16%) and increase in heart rate (mean 22% to 44%) were observed. Hemodynamic effects until 2 hours after nisoldipine administration could be fitted to a sigmoidal Emax model. At times after 2 hours a second effect peak was observed. Cimetidine inhibits the metabolism of nisoldipine but has no significant influence on hemodynamic parameters.
authors.affiliation: Division of Pharmacology, Center for Bio-Pharmaceutical Sciences, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Harten
authors.forename: P
authors.initials: P
authors.lastname: van Brummelen
authors.forename: M T
authors.initials: MT
authors.lastname: Lodewijks
authors.forename: M
authors.initials: M
authors.lastname: Danhof
authors.forename: D D
authors.initials: DD
authors.lastname: Breimer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology*; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D015737:Nisoldipine
chemical_list: D002121:Calcium Channel Blockers; D015737:Nisoldipine; D002927:Cimetidine; D009543:Nifedipine