EVALUATION OF DOSAGE-RELEASE FORMULATIONS ON INHIBITION OF DRUG CLEARANCE - EFFECT OF SUSTAINED-RELEASE AND IMMEDIATE-RELEASE VERAPAMIL ON PROPRANOLOL PHARMACOKINETIC PARAMETERS

Limited information exists regarding the influence of dosage-release f ormulation on inhibition of drug metabolism. Therefore, the purpose of this study was to evaluate the effect of immediate-release (IR) and s ustained-release (SR) verapamil on the pharmacokinetic parameters of p ropranolol in 12 healthy men. IR propranolol, 160 mg, was administered alone (Phase A) and following either IR verapamil, 80 mg t.i.d., (Pha se B) or SR verapamil, 240 mg q.d., (Phase C) in a randomized crossove r fashion. Of the 12 subjects enrolled, only seven were able to be ana lyzed secondary to assay interference. Oral clearances for L-propranol ol for Phases A, B, and C were 198 +/- 70, 156 +/- 76, and 143 +/- 85 L/h, respectively. Oral clearances for D-propranolol for Phases A, B, and C were 203 +/- 96, 172 +/- 96, and 152 +/- 102 L/h, respectively. No significant differences were observed. However, when the verapamil groups (Phase B and C) were combined and compared to Phase A, a signif icant decrease in clearance for propranolol isomers was observed. In c onclusion, due to the unexpected low numbers of patients evaluated, no significant differences in oral clearance were observed among the thr ee treatment phases. However, there is a trend suggesting that SR vera pamil had the greatest effect on propranolol clearance, which may warr ant caution when changing from one formulation to another.