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Biomedical subjects

J Gaillot

Publications and source records attributed to J Gaillot.

At least 37 records · Page 2Linked to original sources
PubMed1985

Carpipramine metabolism in the rat, rabbit and dog and in man after oral administration.

Carpipramine administered orally is excreted via the urine and faeces in rat, rabbit, dog and man. Many metabolites are formed, including several conjugates in the urine. A total of 20-25 metabolites was detected by t.l.c. and h.p.l.c., 16 of which were isolated and identified. Three metabolic pathways were observed: hydroxylation of the iminodibenzyl ring to a phenol or alcohol without modification of the side-chain, hydroxylation of the terminal piperidine of the 2-piperidinol side-chain, and cyclization and dehydrogenation of the same 2-piperidinol group.

Animals↗
PubMed1983

Pharmacokinetics of metapramine (19560 RP) in man after infusion and intravenous injection.

The time course of the plasma level metapramine following infusion at three different rates (1.18, 2.36 and 4.71 mg/h) has been studied in six healthy volunteers. The correlation coefficient of drug concentration and rate of infusion was 0.974 (alpha less than 0.001, n = 18). Plasma clearance, estimated from the steady-state level, varied from 68 to 1071/h. 3 subjects also received 35 mg of drug by i.v. bolus injection and plasma concentrations were determined at set times for up to 24 h. The plasma level of metapramine decreased tri-exponentially, with a terminal half-life of about 7.4 h. The plasma clearance after i.v. injection was in good agreement with that observed during the infusion study. Apparent volumes of distribution ranged from 41.9 to 90.31.

Adult↗
PubMed1983

Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination.

The pharmacokinetics of acebutolol and hydrochlorothiazide (HCT) alone or in combination were studied in 12 healthy subjects in a cross over study. Acebutolol and diacetolol (the main metabolite) in plasma and urine were determined by HPLC and hydrochlorothiazide by GLC. The main pharmacokinetic parameters of acebutolol did not differ significantly: AUC 4492 +/- 272 micrograms l-1h given alone versus 4118 +/- 354 micrograms l-1h with HCT, half-life (7,69 +/- 0,32 h vs 8,10 +/- 0,72 h) and renal clearance (13,1 +/- 0,5 lh-1 vs 13,8 +/- 0,9 lh-1), respectively. There was no difference in diacetolol pharmacokinetics. HCT values were not significantly different: AUC 784 +/- 48 micrograms l-1h given alone and 720 +/- 42 micrograms l-1h with acebutolol, t 1/2 (4,79 +/- 0,37 h vs 4,73 +/- 0,43 h). The renal clearance was slightly higher when HCT was given with acebutolol (26,2 +/- 2,6 vs 20,3 +/- 2,1 lh-1, p less than 0,05). This increase, observed during the first four hours, was probably due to competition between the drugs for binding to red blood cells.

Acebutolol↗
PubMed1983

Pharmacokinetics and metabolism of zopiclone.

Pharmacokinetics and metabolism of a new hypnotic, zopiclone (ZD), were studied under the following conditions: (1) rats and dogs were given oral doses of the molecule, 14C-labeled either on the side chain or on the pyrrolopyrazine nucleus; (2) rats, rabbits and dogs were given increasing oral doses of the cold compound; (3) human subjects in various physiopathological situations--young and elderly healthy volunteers, patients with liver or renal impairments, nursing mothers--were given single or repeated doses, p.o. or i.v. (range 3.5-15 mg). ZD is rapidly and efficiently absorbed: its oral bioavailability was greater than 75% in all species except rats, where a first-pass effect of about 65% was recorded. Plasma protein binding is about 45%. The radioactive material rapidly diffuses from the vascular compartment, with a marked affinity for the brain. Plasma kinetics of ZD are generally well described by a two-compartment open model; in man, terminal half-life is 4-5 h; total body clearance is large (300 ml/mn), renal clearance very low (10 ml/min). The relationship between doses and concentrations, doses and urinary excretion of unchanged compound and major metabolites was linear in all species, except rabbits. The major metabolic routes involve decarboxylation affecting more than 50% of dose (rats and dogs), N-demethylation and N-oxidation--more than 30% as N-desmethyl and N-oxide derivatives in urine (humans). Due to intensive metabolism, only 7-10% of the dose is recovered in urine and feces as unchanged compounds (all species). In nursing mothers, milk and plasma kinetics of ZD are similar with a milk/plasma ratio around 0.80. In human volunteers, plasma half-life of ZD increases with age, while patients with liver or renal impairments show little or no modification of pharmacokinetic parameters.

Administration, Oral↗
PubMed1982

High-performance liquid chromatographic determination of pipotiazine in human plasma and urine.

A high-performance liquid chromatographic method has been developed for the determination of pipotiazine in human plasma and urine. After selective extraction, pipotiazine and the internal standard (7-methoxypipotiazine) and chromatographed on a column packed with Spherosil XOA 600 (5 micrometers) using a 7:3 (v/v) mixture of diisopropyl either--isooctane (1:1, v/v + 0.2% triethylamine and diisopropyl ether--methanol (1:1, v/v) + 0.2% triethylamine + 2.6% water. The eluted compounds are measured by fluorescence detection. The sensitivity of the method was established at 0.25 ng/ml pipotiazine in plasma and 2 ng/ml pipotiazine in urine (C.V. less than 5%). The method has been successfully applied to a pharmacokinetic study following a single oral administration of 10 mg of pipotiazine.

Antipsychotic Agents↗
PubMed1982

[Pharmacokinetics of isosorbide dinitrate administered by intravenous infusion to hypertensive patients (author's transl)].

The pharmacokinetics of intravenous isosorbide dinitrate was investigated in 11 patients with labile hypertension and with normal renal and hepatic functions. The mode of administration (constant rate infusion without loading dose) was chosen in order to minimize side-effects and to approximate clinical conditions. Isosorbide dinitrate levels were measured by electron-capture gas chromatography. The volume of distribution during steady state (Vd beta = 318 +/- 117 I) and the elimination half-life (t1/2 beta = 64.8 +/- 30.5 min) were similar to those found after perlingual and oral administration. Systemic clearance (Cls = 3.80 +/- 1.48 I/min) was high for a drug given intravenously, presumably because of active hepatic extraction, intensive pre-systemic degradation and very active extra-hepatic metabolism. These findings should be compared with the considerable inter-individual variations observed in theoretical plasma concentrations during steady state and with the presence of two pharmacokinetic models (one -- and two -- compartments) in the patients under study. Comparison of the results obtained by the intravenous route with previously published results after perlingual and oral administration indicates the following bioavailability ratios: perlingual/i.v. = 31%, oral/i.v. = 20%, and oral/perlingual = 63%.

Female↗
PubMed1982

High-performance liquid chromatographic method for the determination of plasma and urine metapramine after dansylation.

A high-performance liquid chromatographic method has been developed for the determination of metapramine in human plasma and urine. After selective extraction and derivatization with dansyl chloride, metapramine and the internal standard (maprotiline) are chromatographed on a reversed-phase LiChrosorb RP-18 column using a mixture of water--acetonitrile (35:65) as mobile phase. The eluted compounds are measured using a fluorescence detector. The detection limit of the assay for plasma and urine samples is about 1 ng/ml. The method has been successfully applied in a pharmacokinetic study following intravenous administration of 35 mg of metapramine.

Chromatography, High Pressure Liquid↗
PubMed1982

Pharmacokinetics and metabolism of zopiclone.

Pharmacokinetics and metabolism of a new hypnotic, zopiclone (ZD), were studied under the following conditions: (1) rats and dogs were given oral doses of the molecule, 14C-labeled either on the side chain or on the pyrrolopyrazine nucleus; (2) rats, rabbits and dogs were given increasing oral doses of the cold compound; (3) human subjects in various physiopathological situations - young and elderly healthy volunteers, patients with liver or renal impairments, nursing mothers - were given single or repeated doses, p.o. or i.v. (range 3.5-15 mg). ZD is rapidly and efficiently absorbed: its oral bioavailability was greater than 75% in all species except rats, where a first-pass effect of about 65% was recorded. Plasma protein binding is about 45%. The radioactive material rapidly diffuses from the vascular compartment, with a marked affinity for the brain. Plasma kinetics of ZD are generally well described by a two-compartment open model; in man, terminal half-life is 4-5 h; total body clearance is large (300 ml/mn), renal clearance very low (10 ml/min). The relationship between doses and concentrations, doses and urinary excretion of unchanged compound and major metabolites was linear in all species, except rabbits. The major metabolic routes involve decarboxylation affecting more than 50% of dose (rats and dogs), N-demethylation and N-oxidation - more than 30% as N-desmethyl and N-oxide derivatives in urine (humans). Due to intensive metabolism, only 7-10% of the dose is recovered in urine and feces as unchanged compounds (all species). In nursing mothers, milk and plasma kinetics of ZD are similar with a milk/plasma ratio around 0.80. In human volunteers, plasma half-life of ZD increases with age, while patients with liver or renal impairments show little or no modification of pharmacokinetic parameters.

Administration, Oral↗
PubMed1979

A priori lithium dosage regimen using population characteristics of pharmacokinetic parameters.

The important problem of initiation of long-term lithium treatment is tackled by means of the selection of an a priori dosage regimen based on the presumed efficacy of lithium and absence of toxicity. The pharmacokinetics of Li+ ion is represented by a four-compartment open model including the supposed first-order processes for the release of the active compound from the dosage form and its absorption. Experimental protocols for measurements of serum concentrations and of urinary amounts after single and multiple dosing to healthy volunteers were derived with several oral dosage forms. Estimation of the pharmacokinetic parameters for each subject made it possible to validate the model for the various dosage forms. The interindividual variability of these parameters is taken into account by estimating the characteristics of the statistical distribution for the whole population. A dosage regimen is considered optimum when serum concentration profiles at steady state range from the threshold of efficacy (0.8 mmol/liter) to the threshold of toxicity (2.0 mmol/liter). When the number of daily intakes is fixed, the search for the optimum dose for the whole population is effected by minimizing the expected value of the random variable which characterizes the risks of excursion out of the therapeutic range. By this means universal dosages are shown to be unsatisfactory. However, certain dosage regimens individualized with respect to the renal clearance value of lithium and based on two or three daily intakes can give excellent results even when conventional dosage forms are used.

Adolescent↗
PubMedDate not supplied

Kinetics of metapramine and its demethylated metabolites after single and chronic oral administration in man.

The kinetics of metapramine and two of its demethylated metabolites were determined in six normal subjects after oral administration of a single 150 mg dose on day 1 and 3 X 50 mg dose on day 2-6. This study has shown that three demethylated metabolites are found in plasma beside metapramine. The monodemethylated metabolite I appeared to be the predominant one and the mean area under the plasma concentration curve (AUCo24) was 49% of the metapramine value. Its half-life was shorter (5.92 h) than that of metapramine (8.29 h). The kinetic profiles of metapramine and its major metabolites I and II were similar and data over 24 h could be fitted by a tri-exponential equation even though entero-hepatic cycles were observed. A high interindividual variability of data was found for both metapramine and its metabolites. There were no significant differences between men and women. The minimal plasma level (Cmin) seemed in agreement with the half-life of the drug.

Dibenzazepines↗
PubMedDate not supplied

Chronopharmacokinetic and bioequivalence studies of two formulations of trimipramine after oral administration in man.

The bioavailability of two oral formulations of trimipramine, tablets and solution, was performed in twelve healthy volunteers, in a cross-over study. Each formulation was administered in the morning after a fasted period, and in the evening after a meal, in order to evaluate the role of both administration time and food consumption on the plasma kinetic parameters, under usual therapeutic conditions. A high interindividual variability of data was found. First, the extent of bioavailability was identical for the two formulations but the rate of bioavailability seemed to be different, with the p.o. solution, being more rapidly absorbed (tmax = 1.50 h). The effect of administration time was more obvious for the solution as shown by a lower quantitative absorption as well as a delay in time to reach the maximal concentration. Regardless of formulation and administration time, the t1/2 beta was about 10 hours and the mean MRT value was 11 hours.

Administration, Oral↗