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.
Twelve healthy volunteers received four separate doses of cyclosporin (5 mg kg‐1). On three occasions the neat oil suspension (Sandimmun) was given dispersed in a different liquid vehicle and on one occasion the suspension was taken directly. Measurement of whole blood cyclosporin concentrations by radioimmunoassay showed no significant difference in the pharmacokinetic parameters of absorption between the neat preparation and the three dispersants used (milk, milk + chocolate flavouring and orange juice).
We report a case in which acute digital hydrofluoric acid burns were treated with regional intravenous perfusion of calcium gluconate to relieve pain and protect from further tissue damage. This is the first documented instance of this technique being used. The conventional treatments for digital hydrofluoric acid burns all have their shortcomings; intravenous regional perfusion of calcium gluconate may be an effective method of treatment for digital hydrofluoric acid burns.
The plasma concentration-time profile of verapamil was studied in eight healthy drug-free volunteers after oral administration of a single 80 mg dose of the drug on six separate occasions at different times of day (4 AM, 8 AM, noon, 4 PM, 8 PM, and midnight). The median maximum plasma concentration of verapamil was significantly higher after the 8 AM and noon administrations (p less than 0.05) than at any other time. The median area under the concentration-time curve was also significantly higher (p less than 0.05) after administration at 8 AM and noon than at other times. The median time to maximum concentration was not significantly different at any time point (p greater than 0.05). It is possible that concentration-related adverse effects of verapamil could be avoided by choosing the time of day when the drug is prescribed. This concept may also apply to other drugs that have circadian effects in their pharmacokinetic profiles.
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