title: Bioequivalence and relative bioavailability of a new diltiazem sustained release formulation.
abstract: The bioequivalence and relative bioavailability of a new sustained release formulation of diltiazem (120 mg, Diltiazem-Mepha 120 retard, CAS 33286-22-5) in comparison with a 120 mg reference formulation was investigated in a randomised 2-way cross-over study in 18 healthy volunteers following multiple, twice daily dosing for 5 days. Blood samples were taken prior to the morning dose on days 1 to 4 and before and periodically during 32 h after the last administration in the morning of day 5. The diltiazem concentration was determined using a HPLC method. The following primary and secondary pharmacokinetic parameters were derived from the individual plasma concentration time courses on day 5:Cmax and AUC tau (primary parameters) and PTF,PTS, t1/2, tmax and F(rel) (secondary parameters). For the new test formulation mean (SD) Cmax was 168.9 (49.1) ng/ml and AUC tau was 1343 (313) ng . h/ml, whereas these values were 194.7 (44.2) ng/ml and 1460 (444) ng . h/ml for Cmax and AUC tau of the reference formulation, respectively. Smaller inter-subject variations of the diltiazem plasma concentrations following administration of the test formulation were found, which could be due to an improved retardation principle. However, the point-estimate and 90% confidence interval around the point-estimate fall inside the bioequivalence acceptance range of 0.70-1.43 for Cmax and 0.80-1.25 for AUC tau. Therefore, from the results of this study it can be concluded that the test formulation is bioequivalent with the reference formulation following multiple dose, twice daily administration.
authors.affiliation: Mepha AG, Aesch, Switzerland.
authors.forename: M W
authors.initials: MW
authors.lastname: Scheiwe
authors.forename: G
authors.initials: G
authors.lastname: Lankhaar
authors.forename: C H
authors.initials: CH
authors.lastname: Kleinbloesem
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D012995:Solubility; D013810:Therapeutic Equivalency
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D004110:Diltiazem