Gas chromatographic determination of maprotiline and its N-desmethyl metabolite in human blood using nitrogen detection.
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Biomedical subjects
Publications and source records attributed to A Sioufi.
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A method for the determination of amantadine hydrochloride at concentrations down to 10 ng/ml in human plasma and urine is described. After addition of a known amount of amphetamine sulphate as internal standard to 1 ml of plasma or urine, amantadine is extracted at basic pH in toluene. Both compounds are derivatized with trichloroacetyl chloride. The derivatives are determined by gas chromatography using a 63Ni electron-capture detector. The technique was applied in a study of the elimination of amantadine after oral administration to man; plasma concentrations are reported.
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A method for the determination of benzoic acid down to concentrations of 10 ng/ml in plasma or urine is described. After addition of an internal standard, benzoic acid is extracted at acid pH into diethyl ether. Both compounds are derivatized with pentafluorobenzyl bromide. The derivatives are determined by gas chromatography using a 63Ni electron-capture detector. Hippuric acid is hydrolysed in plasma and urine and total benzoic acid is determined by the same technique.
The determination of alpha-tribenoside at concentrations down to 10 ng/ml and beta-tribenoside at concentrations down to 5 ng/ml in human plasma is described. After addition of an internal standard, alpha- and beta-tribenosides are extracted at basic pH into benzene. Both compounds are derivatized with N-heptafluorobutyrylimidazole. The derivatives are determined by GLC using a 63Ni-electron-capture detector.
Plasma concentration profiles were studied after single and oral doses of phenylbutazone of 100, 300, and 600 mg in cachets to six healthy volunteers. The pharmacokinetics of phenylbutazone can be described by a two-compartment open model. The drug is absorbed rapidly and distributed partially into an extravascular compartment; about one-third remains in the plasma. The mean elimination half-life was 77 hr (54-99 hr), and there was a linear relationship between the dose and the area under the plasma concentration curve. In a multiple-dose study, six healthy volunteers received 150 mg of phenylbutazone in cachets twice daily every 11-13 hr for 17 days. A steady state was reached after approximately 200 hr of chronic treatment. The resultant steady-state plasma concentration were about four times higher than the peak concentration produced by a single 150-mg dose. The half-lives corresponding to the apparent elimination rate constant for the first and last administrations did not differ in each subject. The theoretical minimum concentrations are higher than the pseudosteady state reached during chronic treatment.
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A GLC method for phenylbutazone at concentrations down to 10 ng/ml in human plasma is described. After addition of an internal standard, phenylbutazone is extracted at pH 5 into benzene. The dry extract is dissolved in benzene, and phenylbutazone is determined by GLC using a 63Ni-electron-capture detector.
A method for the determination of free and conjugated triclosan at concentrations as low as 2 ng/ml in human plasma or urine is described. Conjugated metabolites are split by enzyme hydrolysis. After addition of an internal standard, triclosan is extracted at acid pH into petroleum ether, transferred to an alkaline aqueous solution, and back-estracted into petroleum ether after acidification. Both compounds are acetylated with acetic anhydride in the presence of pyridine. The acetyl derivatives are determined by GLC using a 63Ni-electron-capture detector.
Diclofenac and an internal standard are isolated from biological samples by acid-specific extraction and converted into the corresponding indolones with 0.5% sulphuric acid in 2,2,2-trifluorethanol. The neutral derivatives are isolated by solvent extraction and subjected to gas-liquid chromatography. The use of an electron capture detector permits the assay of diclofenac at levels down to 2 ng per sample.
A specific method for the determination of 10 alpha-methoxy-9,10-dihydrolysergol, a nicergoline metabolite (metabolite 2), in urine is described. Metabolite 2 was well separated from the urine components on a reversed phase column, Hypersil ODS 5 microns, using an acetonitrile:pH 3.5 phosphate buffer (40:60, v/v) as the mobile phase at a flow rate of 1 mL/min. UV detection was set up at 220 nm. After addition of a known amount of lysergamide as the internal standard, the compounds were extracted from alkalysed urine on a pre-packed glass column (Extrelut 1) with dichloromethane. With 0.5 mL urine, concentrations down to 0.56 mumol/L could be determined.
Pirprofen (100 or 200 mg; Rengasil) was administered to experimental groups of children (children with juvenile chronic arthritis, JCA) and to a control group of children (children without JCA) as a single dose or as repeated doses. The pharmacokinetics of pirprofen in these children were compared to the pharmacokinetic parameter values obtained in healthy volunteers and in elderly arthritic adults receiving 400 mg of pirprofen. The children were examined regularly and laboratory values were determined in order to detect possible side effects. The results demonstrated that the pharmacokinetics of pirprofen were similar for children and adults when taking into account the dose and the body weight. There was no drug accumulation after repeated administration of pirprofen. As already observed in rheumatic adults, pirprofen remains in synovial fluid longer than in plasma.
Various aspects of bioequivalence are investigated in this paper. Some aspects dealing with bioequivalence studies conducted either during the development of the drug or after its marketing will be presented and discussed: Bioequivalence of highly variable drugs with the associated problem of widening the acceptance range or alternative solutions. Bioequivalence for the final market image. Bioequivalence for investigating the food effect. Bioequivalence in special population such as children, non Caucasian population. Bioequivalence based on in vitro data or literature. New approaches in bioequivalence interpretation. Bioequivalence and analytical methods which are not sensitive or specific enough.
Blood levels of Maprotiline were analysed and their relationship to the clinical response was examined in 89 depressed inpatients, according DSM III criteria for Major Depressive Episode, given the drug treatment for 3 weeks. Maprotiline produced marked decreases in mean MADRS and COVI scale scores by the end of treatment. On day 21, no correlation between blood levels of Maprotiline and MADRS or COVI scores were found when all patients were considered. Nevertheless, significant correlations were observed on day 14 (r = .22; p less than .05 for MADRS and r = .23; p less than .05 for COVI scale). In addition, a significant correlation between MADRS or COVI scale scores and Maprotiline blood levels were observed on days 14 and 21 in subgroups of young patients, severe depression (high scores to clinical global investigations), during of at least 3 months, treated without other drug than Maprotiline and good responders.
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