Pharmacokinetics and pharmacodynamics of two formulations of verapamil.

Abstract

The pharmacokinetics and pharmacodynamics of sustained release verapamil were compared with the conventional formulation in 10 healthy adult volunteers after single and multiple dosing. The mean time of maximum plasma concentrations of verapamil were significantly prolonged and the absorption rate constants significantly reduced after sustained release verapamil on both day 1 and day 10. On day 10 there was no significant difference between formulations in the relative bioavailability of verapamil. However, the area under the plasma concentration‐time curve and maximum concentration (Cmax) for both formulations increased significantly with repeat dosing. On day 10, the difference in Cmax between formulations was significant. The day 10 mean peak/trough plasma verapamil concentration ratio was significantly less following the sustained release dose form. The mean PR interval was significantly prolonged by both formulations on day 1 and day 10. There were no differences between formulations other than a significantly longer PR interval following the conventional formulation 2 h after dosing on day 10.

Does hypercalcaemia or calcium antagonism affect human melatonin secretion or renal excretion?

“…Little is known about this in man. Therefore, we gave verapamil-the most frequently used and studied calcium channel blocker-orally to healthy individuals at a dose resulting in mean plasma verapamil levels similar to those found in healthy volunteers who had been treated with a slow-release preparation of verapamil for 7-10 days at a dose of 240 mg once daily [33,34]. Verapamil failed to affect the serum MT level in experiment B, but raised the urinary excretion of MT by 145%.…”

“…Therefore, we gave verapamil-the most frequently used and studied calcium channel blocker-orally to healthy individuals at a dose resulting in mean plasma verapamil levels similar to those found in healthy volunteers who had been treated with a slow-release preparation of verapamil for 7-10 days at a dose of 240 mg once daily [33,34]. Therefore, we gave verapamil-the most frequently used and studied calcium channel blocker-orally to healthy individuals at a dose resulting in mean plasma verapamil levels similar to those found in healthy volunteers who had been treated with a slow-release preparation of verapamil for 7-10 days at a dose of 240 mg once daily [33,34].…”

Cardiogenic Shock Following a Single Therapeutic Oral Dose of Verapamil

“…In healthy individuals, peak total plasma verapamil concentration after a single 80 mg oral dose is expected to be below 0.15 mg/l 9 . A higher concentration can only be due to an impaired hepatic first‐pass elimination of verapamil.…”

Effects of prototypic calcium channel blockers in methadone-maintained humans responding under a naloxone discrimination procedure

“…Diltiazem was administered 180 min prior to the first post-drug assessment cycle, because the peak affects of diltiazem occur at approximately 3–5 h post-administration (Bottiger et al, 2001). Verapamil was administered 90 min prior to the first post-drug assessment cycle, because the peak affects of verapamil occur at approximately 1–1.5 h post-administration (Hla et al, 1987; Sasaki et al, 1993). Each drug was administered in a double blind and “double-dummy” fashion.…”