A steady-state evaluation of the bioavailability of chronotherapeutic oral drug absorption system verapamil PM after nighttime dosing versus immediate-acting verapamil dosed every eight hours.
To compare the steady state pharmacokinetics of the 200 mg verapamil PM CODAS (chronotherapeutic oral drug absorption system) formulation dosed nightly versus immediate-acting verapamil 80 mg tablets dosed three times daily, an open-label, single-dose, two-treatment, two-period, two-sequence, balanced, randomized crossover study was performed with a 7-day washout between two treatment periods. Twenty-four healthy male subjects completed the study. All subjects received CODAS verapamil PM 200 mg under fasting conditions dosed at nighttime or verapamil 80 mg dosed three times daily at 8-hour intervals in a randomized fashion. CODAS verapamil PM 200 mg dosed at night for 5 days results in a plasma profile with a lag time of approximately 4 hours suitable for nighttime dosing. Significantly lower plasma concentrations of both enantiomers of verapamil and norverapamil resulted in lower peak-to-trough fluctuations and should ensure the safety of the product. Both medications tested in this study were well tolerated by the group of healthy volunteers.
Prisant
L M
LM
Section of Cardiology, Medical College of Georgia, Augusta, GA 30912-3105, USA. mprisant@mailmcg.edu
Devane
J G
JG
Butler
J
J
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019454:Chronotherapy; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D012016:Reference Values; D014700:Verapamil / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D014700:Verapamil