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.
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.
A randomized crossover study was carried out in 7 healthy subjects to investigate the pharmacokinetics of indoramin from two oral formulations (film-coated and uncoated 50 mg tablets) and to determine the effect of a standard mean on the plasma concentration time curve of the film-coated form. The results indicated that peak plasma concentrations occurred in 1 to 4 hours after treatment with a single dose of 2 tablets, with an overall elimination half-life of 5 hours. No significant differences could be shown between treatments in any of the pharmacokinetic variables determined. However, administration of film-coated indoramin after a standard meal narrowed the range of peak concentrations but the time at which peak concentrations of the drug occurred did not appear to be related to whether or not indoramin was given after the meal.
A multi-centre, double-blind, double-dummy trial was carried out in general practice to compare the effectiveness and tolerance of oral meptazinol with dextropropoxyphene/paracetamol in patients with acute or chronic painful conditions. Patients received doses of 400 mg meptazinol or 65 mg dextropropoxyphene plus 650 mg paracetamol every 3 to 6 hours as required up to a maximum of 4 doses per day over a period of 14 days. No significant difference in analgesic efficacy, as assessed by the patients on a visual analogue pain rating scale, was found between the two treatments. The results are discussed in terms of the benefit/risk ration of polypharmic and single compound drugs.
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