Pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium after oral administration to man

Abstract

A method has been developed for the quantitative determination of heptabarbital [5-(1-cyclohepten-1-yl)-5-ethylbarbituric acid] in human plasma after administration of single therapeutic doses of the drug. It involves a single extraction step followed by gas chromatography with alkali flame ionization detection, and the results were linear in the concentration range 0.125 - 5.0 mug/ml plasma. The pharmacokinetics and relative bioavailability of heptabarbital and heptabarbital sodium were studied in a crossover design in 7 healthy volunteers after oral administration of 20 tablets containing 200 mg heptabarbital and hard gelatine capsules containing an equivalent amount of its sodium salt. Heptabarbital concentrations in plasma were determined at regular intervals. The absorption of heptabarbital from the tablets absorbed more rapidly and peak concentrations occurred between 1/3 and 2 h. In all cases the elimination of heptabarbital could be described by a single first-order process with an average half-life of 7.6 h (range 6.1 - 11.2 h). The half-life of the drug in each individual was about the same in the two trials. The relative bioavailability in each volunteer was estimated by comparing the areas under the plasma concentration curves. The sodium salt had an average bioavailability of 83% relative to the free acid. In some volunteers urinary excretion of unchanged heptabarbital was measured; cumulative excretion amounted to 0.16 - 0.30% of the administered dose. Four volunteers received one tablet each night for eight or ten days, but no accumulation was found. In three volunteers the half-life of the drug prior to and after these experiments did not change, whereas in the other volunteer the half-life decreased from 7.1 to 4.6 h. The possibility of enzyme induction should be considered when heptabarbital is taken regularly. It was concluded that heptabarbital was a suitable drug for the treatment of insomnia, since its half-life was rather short. Heptabarbital sodium may be used for induction of sleep, whereas Medomin tablets, i.e. heptabarbital free acid, may be prescribed when the maintenance of sleep is the primary reason for treatment with a hypnotic drug.

Absolute Intramuscular, Oral, and Rectal Bioavailability of Alizapride

“…In the present investigation, the stability profiles between the two metastable forms of phenylbutazone are comparatively evaluated. The preparation and characterization of the phenylbutazone polymorphism have been described previously (9)(10)(11)(12)(13)(14)(15)(16)). The polymorphic system has been reported to consist of a stable form (form b), four metastable forms (forms a, B, y, and c), and two pseudopolymorphs, among which form c has the highest solubility.…”

Pharmacokinetic Determinants of Drug Abuse and Dependence

“…Rapid and complete absorption are associated with a rapid onset of the effects of that drug (Breimer & de Boer 1975); drugs with these characteristics will be preferred to the ones where absorption rate is slow and the subjective effects of the drug are therefore diminished or eliminated. For example, diazepam is more rapidly absorbed than oxazepam; this property and its high bioavailability may partly help explain the clinical observation that diazepam is preferred over other benzodiazepines by drug abusers (Busto et al 1983;Griffiths et al 1984;Stitzer et al 1981).…”