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Biomedical subjects

G Houin

Publications and source records attributed to G Houin.

At least 145 records · Page 8Linked to original sources
PubMed1989

High performance liquid chromatographic method for routine monitoring of amiodarone and desethylamiodarone plasma levels.

The authors describe a normal phase liquid-chromatographic assay suitable for therapeutic monitoring of amiodarone and desethylamiodarone in human plasma. The compounds were extracted at pH 3.8 into methyl tert-butyl ether containing [2-ethyl-3-3.5-dibromo-4-dipropylaminoproxybenzoyl)benzothiophe ne] as internal standard. The separation was obtained by using a mobile phase of methanol-methyl tert butyl ether-sulfuric acid (60-40-0.015; v/v/v). The absorbance of the compounds was monitored at 254 nm with a sensitivity limit of 0.05 mg/l for amiodarone and 0.02 mg/l for desethylamiodarone. The mean overall recovery from plasma samples was greater than 90 p. cent for both compounds. This method was applied to therapeutic and pharmacokinetic studies.

Amiodarone↗
PubMed1989

Rapid quantitative determination of doxorubicin and its metabolites in biological samples.

A rapid sensitive and selective method is developed for the plasma analysis of doxorubicin and its metabolites, doxorubicinol and doxorubicinone with daunorubicin as the internal standard, by using high performance liquid chromatography (HPLC) with fluorescence detection and a "zorbax ODS" column. An eluent containing tetrahydrofuran and trietylamine afforded improved efficiency and resolution and was used to resolve the four anthracycline derivatives in a sole isocratic run. An example of the plasma levels obtained in a cancerous patient after two different administrations is shown.

Chromatography, High Pressure Liquid↗
PubMed1989

Pharmacodynamics and pharmacokinetics of dermatan sulfate in humans.

Dermatan sulfate (DS), a catalyst of the thrombin-heparin cofactor II interaction, has antithrombotic activity and is devoid of significant hemorrhagic risk in several animal models. We investigated the pharmacodynamic and pharmacokinetic properties of DS in humans. DS was injected in single bolus intravenous injections of four increasing doses (0.5, 1, 1.5, 2 mg/kg) to six healthy volunteers. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (APTT) and the thrombin clotting time (TCT). There were dose-dependent prolongations of the APTT and TCT, and the anticoagulant activities disappeared in less than three hours. The pharmacokinetic parameters were calculated from the plasma concentrations of DS measured with a new chromogenic assay. The volume of distribution was approximately 1.8 times greater than the theoretical plasma volume and was independent of dose. In contrast, the clearance decreased with dose and the terminal half-life ranged from 0.45 +/- 0.08 hours at 0.5 mg/kg to 0.72 +/- 0.11 hours (mean +/- SD) at 2 mg/kg. The bioavailabilities of subcutaneous (SC) and intramuscular (IM) administration relative to those of intravenous administration were determined in 12 other volunteers. The respective bioavailabilities were 24.7% +/- 12.9% and 12.4% +/- 9.2% for SC and IM administration. There was no detectable change in the APTT and the TCT when the volunteers were injected with 1.5 mg/kg SC or IM. In addition, the pharmacokinetic parameters derived from plasma concentrations of DS showed considerable interindividual variations by the two later routes of administration. Peak concentrations were noted 2.7 +/- 1.3 hours after SC injection and 4.3 +/- 4.9 hours after IM injection. The average peak concentrations were 0.7 +/- 0.3 and 0.4 +/- 0.2 mg/L after SC and IM injections, respectively. The half-lives of DS were 7.9 +/- 6.5 hours (SC) and 6.3 +/- 7.4 hours (IM). No adverse reaction to DS was recorded during this study.

Adult↗
PubMed1988

Pharmacokinetics of dermatan sulfate in the rabbit after intravenous injection.

To investigate the pharmacokinetic properties of dermatan sulfate (DS), a new potential antithrombotic agent, two different approaches were used. In the first one, DS was derivatized with 3-4 hydroxyphenyl propionic acid N hydroxysuccinimide ester (SHPP) and iodinated. The labelled derivative was injected by IV route to rabbits with increasing doses of unlabelled compound ranging from 20 to 4000 micrograms/kg. The disappearance of DS from plasma was characterized by measuring both the circulating radioactivity and the biological activity using an original assay based upon the catalysis of heparin cofactor II - thrombin formation. The radioactivity data indicated that the volume of distribution, the clearance and the half life of the tracer were independent of the dose of DS injected. DS concentrations measured by the bioassay indicated that more than 90% were cleared with half lives close to those calculated from the radioactivity data; the remaining biological activity was cleared at a slower rate. Experiments performed with bi-nephrectomized animals indicated that the kidneys play a major role in the elimination of DS or of its metabolites which may have a residual biological activity. In the second set of experiments, unlabelled DS was delivered under continuous intravenous infusion for 5 hours at 5 increasing doses ranging from 160 to 4200 micrograms/kg/h. The biological activities were used to measure the plateau concentration of DS: there was a linear relationship between the dose delivered and the plasma concentration. These data indicate that the pharmacokinetic profile of DS is very close to that of low molecular weight heparin, and quite different from that of SH.

Animals↗
PubMed1988

Pharmacokinetics of veralipride after chronic administration in humans.

A pharmacokinetic study of veralipride (N-[(1-allyl-2-pyrroli dinyl)methyl]-5-sulfamoyl-o-veratramide) was performed in healthy volunteers during a chronic administration. The pharmacokinetic model based on the hypothesis of a double site for drug absorption, previously used after a single-dose oral administration, was developed to fit the data obtained after chronic administration. The empirical model used allows correct depiction of the behavior of the drug in the body, especially secondary peaks. According to the results, veralipride pharmacokinetics did not show any change upon chronic administration.

Adult↗
PubMed1988

Prednisolone binding to plasma proteins in domestic species.

The binding of prednisolone to total plasma proteins of dogs, horses, cows, and sheep was characterized using equilibrium dialysis. Prednisolone was bound to a first protein with high affinity but low capacity (transcortin) and to a second protein according to a nonsaturable mechanism (albumin). Interspecies differences were observed, with cows and dogs exhibiting the lowest, and sheep and horses the highest specific binding capacities. The results are in good agreement with known pharmacokinetic properties of prednisolone in domestic species.

Animals↗
PubMed1988

The pharmacokinetics of bendazac-lysine and 5-hydroxybendazac, its main metabolite, in patients with hepatic cirrhosis.

We have studied the pharmacokinetics of bendazac and its major metabolite, 5-hydroxybendazac, in 11 patients with hepatic cirrhosis after the oral administration of a single 500 mg tablet of bendazac-lysine, and compared them with those obtained from 10 healthy adults. The rate of absorption of bendazac, as assessed by tmax and Cmax, is similar in patients and in healthy subjects. The drug is eliminated mostly by metabolism in healthy adults, more than 60% of the dose being excreted in the urine as 5-hydroxybendazac and its glucuronide. Hepatic insufficiency impairs this metabolism, a two-fold decrease in apparent plasma clearance (CL/f) being observed in the patients. Although the plasma unbound fraction of bendazac is increased in patients (the drug is highly bound to plasma albumin), the apparent volume of distribution (V/f) is unchanged. In consequence, the half-life of bendazac is increased two-fold in the patients. Impairment of metabolism decreases the formation of 5-hydroxybendazac, but metabolism remains the main route of its elimination. Renal excretion of bendazac accounts for about 10% of the dose in both patients with cirrhosis and healthy subjects. We conclude that in patients with severe hepatic insufficiency the daily dose of bendazac-lysine should be halved.

Adult↗
PubMed1988

Clinical pharmacokinetics of doxycycline and minocycline.

Doxycycline and minocycline are second-generation tetracyclines. They are readily absorbed, distributed throughout the organism as a function of their lipophilicity and eliminated in both the urine and the faeces. The influence of age, renal disease, malnutrition and hyperlipidaemia is reviewed, together with the main pharmacokinetic interactions.

Adolescent↗
PubMed1987

Pharmacokinetics of bendazac-lysine and 5-hydroxybendazac in patients with renal insufficiency.

The pharmacokinetics of bendazac and its major metabolite, 5-hydroxybendazac, have been investigated in 15 patients with moderate to severe renal insufficiency and renal failure following a single oral dose of 500 mg bendazac-lysine. The pharmacokinetic parameters were compared to those obtained in 10 healthy adult volunteers. The rate and the extent of absorption of bendazac was not modified in the patients with moderate and severe renal insufficiency, nor was there any change in plasma tmax, Cmax, apparent elimination t1/2 and AUC. There was a significant increase in the unbound fraction of bendazac in renal failure patients undergoing haemodialysis, with a consequent increase in the apparent volume of distribution (V/F) and apparent plasma clearance (CL/F), and a decrease in plasma Cmax and AUC. Simultaneous changes of V/F and CL/F lead to an unchanged plasma t1/2 in these patients. Renal clearance (CLR) was decreased, but CL/F was not affected, since renal excretion is a minor route of elimination of bendazac. Bendazac is mostly eliminated by metabolism to 5-hydroxybendazac, in healthy subjects greater than 60% of a dose being excreted in urine as 5-hydroxybendazac and its glucuronide. In patients with renal insufficiency urinary excretion of 5-hydroxybendazac was decreased and the systemic availability of the metabolite (AUC), was increased about three-fold, irrespective of the degree of renal failure. Plasma 5-hydroxybendazac glucuronide accumulated according to the degree of renal insufficiency. Overall it can be assumed that the pharmacological effect of the drug will not be enhanced in renal failure and that the dosage regimen of bendazac-lysine in such patients need not be modified.

Adult↗
PubMed1987

A double-peak phenomenon in the pharmacokinetics of veralipride after oral administration: a double-site model for drug absorption.

Equal doses of veralipride have been given to 12 healthy volunteers by three different administrations--intravenous infusion, oral solution, and oral capsules--in a randomized cross-over design. After the intake of the solution, but not after infusion or capsules, two maximum plasma concentrations have been observed and interpreted, according to a double-site model for drug absorption.

Administration, Oral↗
PubMed1987

Pharmacokinetics of erythromycin in patients with severe cirrhosis. Respective influence of decreased serum binding and impaired liver metabolic capacity.

Pharmacokinetic parameters were studied after i.v. infusion of erythromycin (500 mg) in five patients with alcoholic cirrhosis and six normal subjects. Serum AAG levels were 4.7 +/- 2.4 mumol l-1 in cirrhotics and 10.3 +/- 2.1 +/- mumol l-1 in normals. The unbound fraction (fu) of erythromycin was significantly higher in cirrhotic patients (58.3 +/- 17.7%) than in normal subjects (30.5 +/- 2.8%, P less than 0.01), and a negative correlation was found between fu values and serum AAG (r = -0.867, P less than 0.01). Due to increase in fu, volume of distribution (Vss) was significantly augmented in cirrhotics (85.5 +/- 23.8 l vs 57.6 +/- 14.8 l, P less than 0.05). Serum clearance of unbound erythromycin (CLu) was significantly reduced in cirrhotic patients (42.2 +/- 10.1 l h-1 vs 113.2 +/- 44.2 l h-1 in normal subjects, P less than 0.01). This led to marked elevation of serum concentrations of unbound drug and was entirely explained by the decrease of non renal (i.e. hepatic intrinsic) clearance (31.6 +/- 7.5 l h-1 in cirrhotics, 98.6 +/- 41.5 l h-1 in normals, P less than 0.02); renal clearance remained unchanged. It is concluded that in cirrhotic patients, low serum AAG levels and reduced liver metabolic capacity may lead to marked changes in pharmacokinetics of erythromycin, and that similar results might be expected for drugs which exhibit the same serum binding and pharmacokinetic behaviour as erythromycin.

Adult↗
PubMed1987

Effect of size and dosage strength on the bioavailability of two diltiazem formulations during repeated administrations in humans.

In angina pectoris, diltiazem is usually prescribed as two 60 mg tablets in the morning and two 60 mg tablets in the evening. In the course of the pharmaceutical development of this drug, it was therefore planned to study an experimental formulation containing 120 mg of diltiazem. On the basis of dissolution tests in vitro, a bioavailability study was initiated to compare the 120 mg experimental formulation to the standard 60 mg tablet. The study was conducted in 12 healthy volunteers who received the 2 treatments (one 120 mg tablet bid for 7 days versus two 60 mg standard tablets bid for 7 days) according to a cross-over design. Blood and urine samples were analysed by HPLC method with a UV spectrophotometric detection (sensitivity: 5 ng/ml). Analysis of variance did not show any significant difference between the two formulations for the following parameters: maximum plasma levels observed at steady-state, area under the curves and unchanged urinary diltiazem. From these results the extent of absorption of the 120 mg experimental formulation can be considered as bioequivalent to the administration of 2 tablets of the 60 mg commercially available diltiazem formulation. The time to peak, however, was delayed in 75% of the subjects with the 120 mg diltiazem tablet, showing that the surface area of the pharmaceutical preparation is of primary importance for drug dissolution and rate of absorption.

Angina Pectoris↗
PubMed1987

Pharmacokinetics of sulphobromophthalein, lidocaine and indocyanine green in the course of subclinical fascioliasis in sheep.

The pharmacokinetics of three drugs proposed for the assessment of liver function: sulphobromophthalein (BSP), lidocaine and indocyanine green (ICG) were determined in sheep four, eight, 12, 16 and 24 weeks after their infestation by an oral administration of 150 metacercariae of Fasciola hepatica. The disposition of BSP was altered by a significant decrease in its total plasma clearance from eight weeks after infection onwards. This change could be related to the low values of the elimination rate constant consistent with a reduced liver cytosolic conjugation of the dye to glutathione. Lidocaine pharmacokinetics were unaffected by parasitism and the only effect on ICG was an increased volume of distribution consistent with the liver hypertrophy caused by the subclinical fascioliasis.

Animals↗