Pharmacokinetics and metabolism of an intravenously administered penem (Sch 34343) in humans.

The pharmacokinetics of Sch 34343, a new broad-spectrum penem antibiotic, was studied in subjects receiving 1 g of 14C-labeled drug by intravenous administration. At the end of a 30-min intravenous infusion, the mean maximum concentration of drug in serum was 39 micrograms/ml for unchanged Sch 34343 and 49 mu eq/ml for total radioactivity. The mean serum half-lives of Sch 34343 were 0.16 h for the distribution phase and 0.80 h for the elimination phase. The total body clearance of Sch 34343 was 7.52 ml/min per kg, and the mean apparent volume of distribution was 525 ml/kg. Over a 4-day period, mean urinary excretion of radioactivity accounted for 87.9% of the dose, and mean urinary excretion of unchanged Sch 34343 accounted for 23.6% of the dose. The total radioactivity in feces on days 0 to 6 accounted for only 0.8% of the dose. In serum from 0.5 and 1 h, unchanged Sch 34343 represented the major radioactive peak, with negligible amounts of several metabolites. In urine, there were at least six metabolites in addition to Sch 34343. The amount of unchanged Sch 34343 accounted for 33% of radioactivity in samples of urine from 0 to 2 h, 22% in urine from 2 to 4 h, 15% in urine from 4 to 8 h, and 0% in urine from 8 to 12 h.

Steady-state bioavailability of dexbrompheniramine and pseudoephedrine from a repeat-action combination tablet.

The steady-state bioavailabilities of dexbrompheniramine and pseudoephedrine were evaluated following multiple-dose administrations of a repeat-action combination tablet containing 6 mg of dexbrompheniramine maleate with 120 mg of pseudoephedrine sulfate every 12 h for 7 d compared with reference standards. The reference standards used in this study were concomitant administration of conventional 2-mg dexbrompheniramine maleate tablets every 4 h and 120-mg pseudoephedrine sulfate repeat-action tablets every 12 h, each for 7 d. Twelve healthy adult male volunteers completed this randomized two-way crossover study. Blood samples for subsequent assay were obtained at frequent time intervals throughout each 7-d dosing phase. Sensitive and specific gas-liquid chromatographic methods were used for the determination of dexbrompheniramine and pseudoephedrine in plasma. Based on the plasma levels, the times to reach steady state were determined. In addition, the major bioavailability parameters (Cmin, Cmax, tmax, and AUC) for days 6 and 7 of dosing were determined and statistically evaluated. The results of this study demonstrate that, at steady state, the repeat-action combination tablet and concomitant administration of the reference standards are bioequivalent.

Pharmacokinetics and metabolism of rosaramicin in humans.

The pharmacokinetics of rosaramicin was studied in subjects receiving 500 mg of the drug (i) by 1-h intravenous infusion, (ii) in solution orally, or (iii) as tablets orally. After intravenous administration, the rosaramicin levels in serum declined rapidly with t1/2S of 0.27 h for the distribution phase and 3.28 h for the elimination phase. The apparent volume of distribution was 3.78 liter/kg, and the total body clearance was 13.41 ml/min per kg, indicating extensive tissue distribution or metabolism or both. Similar pharmacokinetic data were obtained after oral administration of the drug in solution or tablets and after intravenous dosing. The absolute bioavailability of the drug administered orally, in either tablets or solution, was 32 to 39%. The metabolism and excretion of [14C]rosaramicin administered orally were also evaluated in volunteers. The serum area under the curve (infinity) of unchanged rosaramicin was 19% of that of total radioactivity, indicating extensive metabolism of the drug. About 7.0% of the radioactivity was recovered in the urine, and 86.7% was recovered in the feces. Only a small amount of unchanged rosaramicin was present in the urine (7 to 9% of urinary radioactivity), but none was present in the feces. The major metabolite, 20-bis-ureidorosaramicin, represented 17 to 38% of the radioactivity in the urine and 26 to 29% of the radioactivity in the feces.

Comparacion de la biodisponibilidad de una formula micronizada y otra ultramicronizada de griseofulvina en el hombre. / Comparison of the bioavailability of a micronized and other ultramicronized formula in the man

Se comparo la biodisponibilidad de 500 mg de una formula micronizada de griseofulvina, con dos nuevas formulas ultramicronizadas del agente, dos tabletas de 165 mg y una tableta de 330 mg, en 16 voluntarios varones, sanos, segun un protocolo de estudio aleatorio y cruzado. En base a las concentraciones plasmaticas de griseofulvina, medidas a intervalos especificados durante um periodo de 48 horas, se determinaron los principales parametros de biodisponibilidad (area bajo la curva de concentracion plasmatica en funcion del tiempo, concentracion plasmatica maxima y tiempo necesario para alcanzar la concentracion plasmatica maxima), y los mismos se evaluaron estadisticamente. Los resultados demostraron que una tableta ultramicronizada de 330 mg era bioequivalente a dos tabletas ultramicronizadas de 165 mg de griseofulvina y que ambas posologias de griseofulvina ultramicronizada eran bioequivalentes a 500 mg de la formula micronizada de griseofulvina

Comparative bioavailability of a microsize and ultramicrosize griseofulvin formulation in man.

The bioavailability of 500 mg of a microsize formulation of griseofulvin has been compared to two new ultramicrosize griseofulvin formulations, two 165 mg tablets and a 330 mg tablet, in sixteen healthy, male, volunteers in a randomized crossover study design. Based on the griseofulvin plasma levels measured at specified times over a 48-hour period, the major bioavailability parameters (i.e., area under plasma concentration-time curve, maximum plasma concentration, and time to reach maximum plasma concentration) were determined and statistically evaluated. The results showed that one 330 mg ultramicrosize tablet is bioequivalent to two 165 mg ultramicrosize griseofulvin tablets and that either ultramicrosize griseofulvin dosage regimen is bioequivalent to 500 mg of the microsize griseofulvin formulation.

Evaluation of the prison inmate as a subject in drug assessment.

The reasons for exclusion of prisoners from research studies on drugs were based mostly on a relatively limited group of laboratory parameters which could have been detected using a simple battery of screening tests. The answers to a medical history form added little to the evaluation of either the prisoner or student groups, were probably very unreliable, and could be just as well confined to a few selected questions regarding drug history as a matter of record. Students gave appropriate responses to a mood scale measurement test while prisoners characteristically did not comply. Because of a combination of various institutional and sociological factors, prisoners probably represent a special subgroup of research volunteers whose health status may not be representative of the total "healthy" population. They are unlikely to give accurate or reliable responses in testing situations which rely upon reporting of the subjective effects of drugs with regard to tolerance or pharmacologic effect. Studies of investigational drugs where the likelihood of potentiaal risk is significant should be avoided in such populations unless compliance has been assessed adequately.