Evaluation of dosage-release formulations on inhibition of drug clearance: effect of sustained- and immediate-release verapamil on propranolol pharmacokinetic parameters.
Limited information exists regarding the influence of dosage-release formulation on inhibition of drug metabolism. Therefore, the purpose of this study was to evaluate the effect of immediate-release (IR) and sustained-release (SR) verapamil on the pharmacokinetic parameters of propranolol in 12 healthy men. IR propranolol, 160 mg, was administered alone (Phase A) and following either IR verapamil, 80 mg t.i.d., (Phase B) or SR verapamil, 240 mg q.d., (Phase C) in a randomized crossover fashion. Of the 12 subjects enrolled, only seven were able to be analyzed secondary to assay interference. Oral clearances for L-propranolol 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 significant decrease in clearance for propranolol isomers was observed. In conclusion, due to the unexpected low numbers of patients evaluated, no significant differences in oral clearance were observed among the three treatment phases. However, there is a trend suggesting that SR verapamil had the greatest effect on propranolol clearance, which may warrant caution when changing from one formulation to another.
Bleske
B E
BE
Department of Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Welage
L S
LS
Touchette
M A
MA
Edwards
D J
DJ
Rodman
D P
DP
Shea
M J
MJ
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011433:Propranolol / Q000493:pharmacokinetics*; D014700:Verapamil / Q000008:administration & dosage* / Q000494:pharmacology
D003692:Delayed-Action Preparations; D011433:Propranolol; D014700:Verapamil