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Biomedical subjects

G Houin

Publications and source records attributed to G Houin.

At least 199 records · Page 11Linked to original sources
PubMed1980

Erythromycin pharmacokinetics in man.

This study shows that high serum concentrations are reached after either ethylsuccinate or lactobionate erythromycin administration. But the short elimination half-life implies repetitive administration to obtain efficacy, the ideal being represented by continuous infusion.

Administration, Oral↗
PubMed1979

[The pharmacokinetics of nalidixic acid administered parenterally. Towards rational use in severe infections (author's transl)].

Nalidixic acid is effective toward Gram negative infections but its short half-life and potential neurological toxicity explain that its parenteral use is hazardous. Interindividual variations of its pharmacokinetic parameters explain also the absolute necessity of a careful drug monitoring adapted to each patient. The study of plasma kinetics of a single dose of nalidixic acid injected by intravenous route, shows these metabolic variations. With this results, the predicted plasma drug concentrations show that classical dosage regimens are adapted only to a little number of patients. Advantages and inadequacies of a single daily intravenous infusion of nalidixic acid are next analysed.

Bacterial Infections↗
PubMed1978

Clofibrate and enzymatic induction in man.

The oral administration of clofibrate, 1 g per day for 13 days, did not modify the half-life of antipyrine and urinary glucaric acid excretion in five volunteers. Despite the fact that clofibrate is a strong inducer of hepatic microsomal enzymatic activity in the rat, in man it does not increase, at these doses, the metabolism of antipyrine and the urinary elimination of glucaric acid. Rifampicin, 600 mg per day orally for seven days, decreases the plasma steady-state concentrations of chlorophenoxyisobutyric acid, a major metabolite of clofibrate. It seems that the metabolism of clofibrate depends upon inducible enzymatic activity. When rifampicin and clofibrate are administered together, it may be important to increase the dose of clofibrate used.

Adult↗
PubMed1977

[Modification during treatment of the rate of acetylation of isoniazide clinically or biologically detectable hepatic damage (author's transl)].

The rate of acetylation of isoniazid is usually constant in a given subject. The authors report here a case where despite an adjusted initial dose there was a decrease in the rate of acetylation during treatment with INH-rifampicin and ethambutol, without hepatic involvement but accompanied by retrobulbar optic neuritis. The role of ethambutol and/or an overdose of isoniazid are discussed. The technique for its estimation is also described.

Acetylation↗
PubMed1975

A GLC method for estimation of chlorophenoxyisobutyric acid in plasma. Pharmacokinetics of a single oral dose of clofibrate in man.

A GLC method has been developed to measure chlorophenoxyisobutyric acid in plasma after benzol extraction and transformation to its methyl ester, using methyl laurate as the internal standard. Plasma free fatty acids did not interfere with the analysis, but it could not be employed in the presence of salicylates. The method has been employed to study the pharmacokinetics of chlorophenoxyisobutyric acid in man after oral ingestion of a single dose of clofibrate.

Adult↗
PubMedDate not supplied

Comparative bioavailability study of codeine and ibuprofen after administration of the two products alone or in association to 24 healthy volunteers.

The study objective was to compare the bioavailability of codeine and ibuprofen after oral administration of the two drugs alone or in association. The study was performed in three different periods, each separated by a wash-out of 6 days. Plasma concentrations were measured in 24 healthy volunteers after administration of a single oral dose of codeine phosphate (25 mg) and/or ibuprofen (200 mg). Codeine and ibuprofen assays were performed using two different HPLC methods. The relative bioavailabilities of codeine and ibuprofen (alone or in association) were 106 +/- 24% (mean +/- sd) and 101 +/- 19%, respectively. The results obtained demonstrated that bioavailabilities of codeine and ibuprofen were not modified when the two drugs were administrated alone or in association.

Adult↗
PubMedDate not supplied

An improved everted gut sac as a simple and accurate technique to measure paracellular transport across the small intestine.

An improved everted gut sac system has been developed in which the sacs were carefully prepared from rat small intestine and incubated in tissue culture medium. Under these conditions, the tissue showed good morphology at the electron microscope level, and was metabolically active for up to 2 h at 37 degrees C. Mannitol, an established probe of paracellular transport, was transported from the mucosal to the serosal side of the sac tissue. Excellent kinetic data showed that transport was linear up to 75 min and over a wide range of concentrations (0.025 - (10 mM). Mannitol was not detected in the tissue and transport was enhanced by EGTA, confirming the paracellular route of passage. Sacs prepared from colon also showed mannitol transport, but at a slower rate. Comparisons with Caco-2 cell monolayers showed that the everted sacs exhibited higher levels of paracellular transport than the cultured cell line. The improved everted gut sac system is an inexpensive and relatively simple technique with considerable potential as an in vitro tool to study the mechanisms, kinetics and enhancement of drug absorption across the small intestine at different sites and in the colon.

Animals↗
PubMedDate not supplied

Pharmacokinetics of reboxetine in healthy, elderly volunteers.

The pharmacokinetic characteristics of reboxetine, a unique selective noradrenaline reuptake inhibitor (selective NRI) for the treatment of depression, were studied in 12 healthy, elderly volunteers (mean age 81 years +/- 9 years). All subjects received a single 4-mg dose of reboxetine, and plasma reboxetine concentrations were measured by HPLC. Reboxetine was well tolerated by all subjects. Exposure to reboxetine was higher in this group of very elderly subjects, compared with data obtained in a similar study of young, healthy volunteers. Cmax in the elderly was 271 +/- 86 ng/ml, compared with 111 +/- 28 ng/ml in the young subjects after a single 4-mg dose, although in both groups Cmax was observed after 2 h. The AUC infinity was nearly four times that in the younger subjects (8345 +/- 3107 ng.h/ml vs. 2106 +/- 881 ng.h/ml) and the t1/2 was twice as long (24 +/- 6 h vs. 12 +/- 3 h). Renal clearance was also reduced. Reboxetine 8-10 mg/day has been effective and well tolerated in clinical trials in non-elderly depressed patients. The increased exposure to reboxetine observed in our very elderly subjects supports a reduction of the starting dose to 4 mg/day (in two divided doses) in the elderly.

Adrenergic Uptake Inhibitors↗
PubMedDate not supplied

Relation between unbound plasma concentrations and toxicity in a prolonged oral etoposide schedule.

OBJECTIVE: This study was undertaken in order to evaluate the impact of pharmacokinetics on the toxicity of oral etoposide administered daily for 21 days. METHODS: The daily dose was 50 mg/m2. Thirty-two patients 24 males and eight females, 36 76 years old, treated for various tumour types), were evaluated. Blood samples were obtained on day 1 for all patients, and on day 21 for 16 patients. Plasma etoposide concentrations were determined by high-performance liquid chromatography, and etoposide plasma protein binding by equilibrium dialysis. RESULTS: On day 1, the mean value (with coefficient of variation for interindividual variability) for the unbound fraction (fu), area under the concentration versus time curve (AUC), and unbound AUC was 9.8% (59%), 34 mg x h/l (39%), and 3.5 mg x h/l (92%), respectively. The ratio between AUC on day 1 and day 21 ranged between 0.5 and 1.8 (mean 0.9, with CV 33%). The plasma trough unbound concentrations and the unbound AUCs both corresponding to the first administration were significantly higher in the 11 patients who had a severe neutropenia than in the 21 patients who had no or moderate toxicity. However, total etoposide concentrations did not differ between these two groups. A limited sampling strategy using the NONMEM program and a database of 89 patients previously studied was performed. The optimal sampling schedule (i.e. 1, 4, and 24 h after oral etoposide administration) allowed to obtain the AUC accurately on day 1. CONCLUSION: Individual adjustment of oral etoposide based on unbound pharmacokinetics after the first administration appears relevant and feasible.

Adult↗
PubMedDate not supplied

Pharmacokinetics of intravenously administered 125I-labelled human alpha 1-acid glycoprotein.

The volumes of distribution of many acidic drugs have been shown to be close to that of their binding protein, i.e. serum albumin. The distribution of basic drugs mainly bound to alpha 1-acid glycoprotein (AAG) can be questioned with respect to its dependency upon the distribution of this plasma protein. So, a pharmacokinetic study was performed in 7 subjects with human 125I-labelled alpha 1-acid glycoprotein. The steady-state volume of distribution was found to be 5.37 +/- 0.82L. The central volume was 3.23 +/- 0.33L, close to that of plasma volume and the peripheral volume was 2.14 +/- 0.63L. These data allowed the establishment of an equation giving access to the volume of distribution of a basic drug by relating its unbound fraction to physiological distribution of alpha 1-acid glycoprotein. The values yielded by this equation show that the actual and calculated volumes of distribution of basic drugs mainly bound to AAG are discrepant. This protein is thus not the main factor controlling the distribution of basic drugs within the body.

Adult↗