title: Pharmacokinetics and absolute bioavailability of diltiazem in humans.
abstract: Six healthy male volunteers received single doses of diltiazem hydrochloride on three occasions separated by at least 10 days. Modes of administration were: 10-minute intravenous infusion of a 20-mg dose; oral administration of 120 mg in solution form; and oral administration of 120 mg as two 60-mg sustained-release tablets. Diltiazem concentrations were measured by electron-capture gas chromatography in multiple plasma samples drawn during the 36 hours after dosage. Following intravenous administration, mean (+/- S.E.) pharmacokinetic variables were: elimination half-life, 11.2 (+/- 2.1) hours; volume of distribution, 11.1 (+/- 3.0) liters/kg; and total clearance, 11.5 (+/- 0.7) ml/min/kg. Oral diltiazem in solution form was rapidly absorbed, with peak plasma levels attained at 38 (+/- 6) minutes after the dose. Absolute systemic availability averaged 44% (+/- 4%). Oral administration of sustained-release tablets yielded, as predicted, slower absorption, with peak plasma concentrations attained at an average of 165 (+/- 22) minutes after dosage. Thus, oral diltiazem is incompletely bioavailable after oral administration, mainly because of first-pass hepatic extraction.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001552:Benzazepines / Q000378:metabolism*; D001682:Biological Availability; D002849:Chromatography, Gas; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male
chemical_list: D001552:Benzazepines; D003692:Delayed-Action Preparations; D004110:Diltiazem