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Biomedical subjects

J Volk

Publications and source records attributed to J Volk.

26 records · Page 2Linked to original sources

Bioavailability and kinetics of maprotiline.

Six male subjects received simultaneously single 50-mg oral doses of a maprotiline hydrochloride tablet and a trideuterated maprotiline hydrochloride aqueous solution. No side effects or other problems were encountered. The blood levels of unlabeled and isotope-labeled maprotiline for each subject were essentially superimposable. Peak levels, averaging about 50 ng/ml, were attained between 8 and 24 hr after drug. The biologic t1/2 (beta-phase) averaged 58 hr for the unlabeled and 60.5 hr for the labeled drug. The total areas under the curves (extended to time infinity) averaged 3,862 and 3,944 ng . hr/ml for maprotiline and trideuterated maprotiline, respectively (differences between the two are not significant). At the 95% degree of confidence the Westlake confidence limits show less than 10% differences between the formulations with respect to area under the curve data (calculated both to 168 hr and extended to time infinity), peak blood levels, and biologic t1/2s. There were no differences between formulations with respect to times of peak concentrations. Estimates were made for apparent volumes of distribution (about 1,000 l), apparent blood clearance (about 14 l/hr), lag times (about 1.42 hr for tablets and 1.31 hr for solution), and absorption rate constants (about 0.34 hr-1 for the tablets and 0.42 hr-1 for the solution).

Adult↗

A sensitive method for the simultaneous determination in biological fluids of imipramine and desipramine or clomipramine and N-desmethylclomipramine by gas chromatography mass spectrometry.

A procedure is described which permits the simultaneous determination of imipramine and desipramine or clomipramine and N-desmethylclomipramine in serum or plasma for concentrations in the range of 1-200 ng ml-1. Detection limits of 0.2 ng ml-1 for imipramine and 0.1 ng ml-1 for desipramine were demonstrated with a signal-to-noise ratio maintained at 2:1 or better. The method relies on the derivatization of the secondary amines with heptafluorobutyric anhydride and is based on the combined use of gas chromatography, electron impact mass spectrometry and computerized data handling. The assaying procedure is specific, accurate and precise. It is suitable for routine analyses and has sufficient sensitivity to permit monitoring the drug and metabolite levels in human plasma or serum resulting from a single therapeutic dose.

Chromatography, Gas↗

Metabolism, plasma or serum levels, and elimination of phenformin in guinea pigs, rats, and dogs.

14C-Phenformin hydrochloride was used for investigating the metabolism, plasma or serum levels, and elimination of the drug following 1.5-mg/kg po or iv doses to guinea pigs, rats, and dogs. The amounts of individual metabolites and unchanged drug were assessed in urine as well as in plasma or serum. The glucuronide of 1-(p-hydroxyphenethyl)biguanide was a major metabolite in the blood and urine of all three species. Guinea pig serum and urine contained a sizable quantity of unchanged drug. Dog plasma and urine had significant amounts of nonconjugated 1-(p-hydroxyphenethyl)biguanide and of an unidentified major metabolite. In all three species following intravenous drug administration, unchanged drug contributed significantly to the radioactivity found in blood and urine. The apparent half-lives of phenformin eliminateion were 0.3-0.8 day for guinea pigs and rats and 1-1.5 days for dogs. Urinary excretion data indicate apparent half-lives of approximately 1.3-1.5 days for the elimination of each of the three major metabolites in dogs.

Animals↗

Conversion of biguanides into substituted s-triazines assayable by GC or mass fragmentography.

Substituted s-triazines were prepared by the treatment of biguanides with various organic acid anhydrides. This reaction permits the ready conversion of the hypoglycemic drugs phenformin, buformin, and metformin and of other analogous biguanides into compounds suitable for GC and mass fragmentographic determination with a high degree of sensitivity. Mass spectral data and Kováts retention indexes are presented for all s-triazines prepared for this study.

Biguanides↗