[Bioavailability of two verapamil formulations following repeated administration in steady-state conditions. An open, two-period, crossover study]. 1996

B Heintz, and A Müller, and G Lenhard, and M Schütz, and H J Hutt
Medizinische Klinik II, Rheinisch-Westfälische Technische Hochschule Aachen.

The relative bioavailability of a new formulation of verapamil (CAS 52-53-9, Veramex 40) in comparison to a standard formulation was investigated in an open two-period cross-over study in 16 healthy volunteers under steady state conditions of 7 days duration each. For the estimation of verapamil a selective HPLC-method was used with fluorescence detection after direct injection and enrichment by column switching enabling a simultaneous separation and analysis of verapamil and N-norverapamil. The bioavailability was estimated using areas under the concentration-time curves (AUC), maximum serum concentrations (Cmax) and peak-trough fluctuation (PTF). Bioequivalence was tested calculating the 90% confidence intervals (ANOVAlog). The mean verapamil plasma profile after the test substance was up to 1.5 h slightly lower than the corresponding curve after the reference substance, thereafter slightly higher plasma levels up to 7 h were observed after the test substance. The individual plasma profiles had a similar variance, and hardly any difference was discernible between the two drugs. A similar behaviour was also seen for N-norverapamil. A mean relative bioavailability of 101% was observed after the test substance both for verapamil and N-norverapamil. The mean maximum plasma concentrations for verapamil and N-norverapamil were 50.0 and 49.7 ng/ml, respectively. After the standard formulation the corresponding values were 50.4 and 50.3 ng/ml. The mean PTF-values for verapamil and N-norverapamil were 178 and 76.6% after the test substance and 182 and 79.6% after the standard formulation, respectively. The 90% confidence intervals for AUC, Cmax and PTF for verapamil and N-norverapamil are completely within the accepted range of 80 to 125% for AUC, Cmax and PTF. Therefore bioequivalence between both formulations can be stated.

UI MeSH Term Description Entries
D008297 Male Males
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D013050 Spectrometry, Fluorescence Measurement of the intensity and quality of fluorescence. Fluorescence Spectrophotometry,Fluorescence Spectroscopy,Spectrofluorometry,Fluorescence Spectrometry,Spectrophotometry, Fluorescence,Spectroscopy, Fluorescence
D013810 Therapeutic Equivalency The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease. Bioequivalence,Clinical Equivalency,Equivalency, Therapeutic,Generic Equivalency,Clinical Equivalencies,Equivalencies, Clinical,Equivalencies, Therapeutic,Equivalency, Clinical,Therapeutic Equivalencies,Bioequivalences,Equivalencies, Generic,Equivalency, Generic,Generic Equivalencies
D014700 Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Iproveratril,Calan,Cordilox,Dexverapamil,Falicard,Finoptin,Isoptin,Isoptine,Izoptin,Lekoptin,Verapamil Hydrochloride,Hydrochloride, Verapamil

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