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Biomedical subjects

G Houin

Publications and source records attributed to G Houin.

At least 181 records · Page 10Linked to original sources
PubMed1984

Kinetics of urinary furosemide elimination in infants.

Using a one-compartment model, the urinary elimination kinetics of a single intravenous 1 mg/kg dose of furosemide (F) was studied in 13 infants, 9 days to 12 months old (mean 3.7 +/- (SD) 3.48 months old), and 1, 23-month-old child, with bilateral multifocal pneumonia, recovering from respiratory and cardiac insufficiency accompanying pneumonia and/or other diseases. F elimination half-life was determined with the use of a noninvasive method based on the drug's urinary excretion data. The drug urinary elimination t1/2 in the infants ranged from 0.654 to 3.29 h. Cumulative excretion of F in the infants' urine was similar to the values in healthy adults. Since the furosemide urinary half-lives found in infants were similar to the data reported in older children and healthy adults it is suggested that immaturity of renal function during the 1st year of life, i.e. in older infants, has no evident on the elimination kinetics of a 1 mg/kg intravenous dose of F. Mean F urinary elimination t1/2 in infants with pneumonia and cardiac insufficiency was significantly longer compared with the Ft1/2 found in children with the pneumonia alone (2.15 vs. 1.01 h, respectively), suggesting slower elimination of the drug in these patients.

Anti-Bacterial Agents↗
PubMed1984

Butofilolol pharmacokinetics in chronic renal insufficiency.

The pharmacokinetics of butofilolol, a new beta-blocking drug used in the treatment of hypertension, were investigated in 9 patients with varying degrees of renal impairment (creatinine clearance ranging from 65 ml/min to 6.6 ml/min). The drug was administered as a single oral 100-mg dose. Plasma and urine concentrations of the parent drug were measured. The pharmacokinetic parameters of butofilolol calculated from examination of patients with renal failure were compared to those obtained from healthy subjects. Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent drug whereas its elimination rate constant tended to increase, especially in severe renal failure. A highly significant relationship between the amounts of unchanged drug excreted in urine and the creatinine clearance was observed (r = 0.90, p less than 0.001). The higher plasma levels of the parent drug observed in renal failure might be due to a decrease in the first-pass hepatic extraction of the drug. But these changes in plasma clearance were probably counteracted by modification of the volume of distribution, so that the net result of these alterations was a slight increase in the elimination half-life.

Adrenergic beta-Antagonists↗
PubMed1984

Pharmacokinetics of butofilolol (CAFIDE) after repeated oral administration in man.

The pharmacokinetics of butofilolol, a new beta-blocking drug, was studied in 6 healthy subjects. Plasma concentrations and urinary excretion of the unchanged drug were determined after a single 100-mg oral administration, and also during chronic treatment (100 mg/day for a week) and after the last dose. Maximum plasma concentrations were observed 2 to 3 h after drug administration and varied between the subjects (120 to 430 ng/ml). The apparent volumes of distribution were large, ranging between 200 I and 500 I, and the apparent clearances of elimination appeared to be intermediate between 40 and 70 l/h. Drug elimination in the urine (about 4% of administered dose) occurred by filtration, tubular secretion and pH-sensitive reabsorption following a non-linear process. However, pharmacokinetic parameters remained constant during chronic treatment, since urinary elimination of the parent drug was too low to influence its pharmacokinetic profile. In addition, a high correlation was found between plasma levels of butofilolol and the effect of the drug on resting heart rate, while a slight effect on diastolic blood pressure could be discerned.

Administration, Oral↗
PubMed1984

[Comparison of bacteriological and immunoenzyme methods for the serum determination of sisomicin. Pharmacokinetic application in the human].

A modification of the serum gentamicin immunoenzymatic method (Syva- Biom erieux kit) for sisomicin assay is proposed and compared to the bacteriological reference method. It shows a higher sensitivity (0.1 mg.l-1) with a shortened time of analysis (less than 1 hour) and a good reproducibility (range: 4.7% to 1.6% for concentrations between 0.5 mg.l-1 and 10 mg.l-1) but the concentrations are 15 p. cent lower as compared to the bacteriological method. A pharmacokinetic study, performed in five patients, enables us to demonstrate the praticability of this method for the adaptation of the dosage regimen in renal insufficiency.

Biological Assay↗
PubMed1983

Comparison of gas chromatographic--electron-capture detection and high-performance liquid chromatography for the determination of butofilolol in biological fluids.

Two selective and sensitive methods for the quantitative analysis of butofilol in human plasma and urine are discussed. The first method is a gas chromatographic assay with electron-capture detection using extraction with toluene, several clean-up procedures and derivatization. The second method is based on high-performance liquid chromatography and a single extraction with dichloromethane. The two assay methods were applied to the determination of the same human plasma samples after administration of a single, oral 200-mg dose of butofilolol. A good correlation between the results (inter-laboratory comparison) is obtained, validating both techniques.

Chromatography, Gas↗
PubMed1983

High-performance liquid chromatographic determination of alizapride, a new antiemetic compound, and its application to a dose-dependent pharmacokinetic study.

An assay was developed to measure alizapride (a new antiemetic compound) in biological specimens. The method involved reversed-phase high-performance liquid chromatography and fluorescence detection. The detection limit was 5 ng/ml in plasma or urine samples. The value of the assay was demonstrated with a dose-dependent pharmacokinetic study. It showed a two-phase decrease in plasma concentrations, after intravenous injection, with half-lives of 7.5-min and 2.5-hr, respectively. From plasma and urine results, pharmacokinetic parameters remained constant in the dose range of 50-200 mg.

Administration, Oral↗
PubMed1983

Pharmacokinetic studies of rifampicin in the elderly.

The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1.72 mg L-1 and 4.09 +/- 2.59 h, respectively. They are comparable to those reported in young adults. The same applies to the Cmax value (1.93 +/- 0.53 mg L-1) and t 1/2 beta value (4.65 +/- 2.61 h) of DA-RMP. However, the renal clearance of RMP (0.0075 +/- 0.0036 L h-1) and the amounts of RMP (20.7 +/- 9.9 mg) and DA-RMP (13.3 +/- 5.6 mg) excreted in the urine during a 24-h period are lower than those reported in young adults. The renal excretion of RMP and DA-RMP, therefore, is reduced in the elderly. But since the drug is also excreted through the liver to such an extent that serum levels are the same as in young adults, for therapeutic purposes the metabolism of RMP may be globally considered as unaltered in elderly patients.

Aged↗
PubMed1983

Pharmacokinetics of rifampicin and desacetylrifampicin in tuberculous patients after different rates of infusion.

Four rates of rifampicin infusion ranging from 3.3 to 15 mg/min in 12 tuberculous patients were studied. Blood samples (n = 10) were drawn during infusion and 8 h later. Urine samples were collected in six fractions during a 24-h period. Rifampicin and desacetylrifampicin were measured by high-pressure liquid chromatography. Results show that the maximum plasma concentrations increase linearly for each dose with the rate of infusion, and that the amounts excreted in the urines are highly dependent on the administered dose. Simulation of plasma concentrations after different dosage regimens shows that a double rate of infusion--20 mg min-1 during 1 h and then 200 mg h-1--allows plasma concentrations to be quickly reached and maintained at a 20 mg L-1 level, far higher than the minimum inhibitory concentrations of most germs.

Adult↗
PubMed1983

The effects of chronic renal insufficiency on the pharmacokinetics of doxycycline in man.

The pharmacokinetics as well as erythrocyte and plasma protein binding of doxycycline were studied in fifteen patients with various renal function impairments after oral doxycycline polyphosphate single administration. Plasma half-life (t 1/2), area under the plasma concentration-time curve (AUC), urinary excretion, renal clearance, erythrocyte and plasma protein binding (%) were regressed vs creatinine clearance. No significant correlations were observed between t 1/2 or AUC and renal function nor plasma protein binding and plasma albumin concentrations. Significant correlations were obtained between urinary excretion, renal clearance, erythrocyte binding, plasma protein binding and creatinine clearance. Significant correlation was obtained between haematocrit and erythrocyte binding. Constancy of overall elimination parameters in renal failure is due to parallel increase in plasma free fraction of doxycycline.

Adult↗
PubMed1983

Disease-induced modifications of drug pharmacokinetics.

This article attempts to help in the understanding of the mechanisms responsible for a modified drug pharmacokinetic profile in disease states. The main factors influencing the fate of the drug as it moves from the site of administration to the sites of elimination are depicted. Changes in absorption kinetics can be due to altered gastrointestinal peristalsis and secretions as well as modifications of splanchnic blood flow. Pathological states may affect the binding of drugs to plasma proteins, mainly human serum albumin and alpha 1 acid glycoprotein. The resulting modifications in the free fraction of the drug can cause a change in the volume of distribution. The distribution can also be influenced by circulatory disorders modifying local blood flows and thus impeding drug entry into the tissues. Many diseases can alter hepatic and/or renal clearance. This is not surprising since the elimination mechanisms are dependent upon many factors such the enzymatic status of the liver, plasma protein binding, and blood flow to both the liver and the kidney. Some examples such as the modification of furosemide pharmacokinetics in acute renal failure, the impaired metabolism of opiate analgesics in hepatic insufficiency, the alterations of the usual disposition process in salicylic acid intoxication, and the influence of cardiac failure upon some drugs pharmacokinetics, have been chosen to illustrate some of the aspects discussed. Some simple rules for making a rational selection of drugs in pathological states are also outlined.

Acute Kidney Injury↗
PubMed1983

[Changes in the isoniazid inactivation index during antituberculosis treatment in children].

Fluorimetric assays of serum isoniazid levels were performed in children treated either with isoniazid alone, or with isoniazid associated with other antituberculous drugs, in order to adjust the dosage. Study of the inactivation index at the 3rd hour, showed a faster metabolism in the younger children. Assays repeated twice or more in 160 patients, showed important variability in the results. The variation coefficient was 18,6% for the whole group and above 25% in 25% of cases. The younger age and the association of several other drugs (corticosteroids and possibly erythromycine) may be responsible, at least partly, for this variability. However, association with antituberculous drugs (ethambutol, rifampin) does not seem to change significantly isoniazid metabolism. The magnitude of these variations should lead to a greater caution in the interpretation of isolated isoniazid dosages.

Adrenal Cortex Hormones↗
PubMed1983

Pharmacokinetic study of two pharmaceutical preparations containing alkaloid vincamine administered orally to human subjects.

In a crossover study of six healthy volunteers the pharmacokinetics and the bioavailability of vincamine were studied after administration of two oral forms. All subjects received an oral dose of 60 mg vincamine. The plasma concentrations of the drug were determined by a specific and sensitive gas chromatographic method. In this kind of subject the drug generally follows a one-compartment kinetic model. The average value of Tmax is 1.4 +/- 0.5 h-1 with the tablets and 1 +/- 0.6 h-1 with the solution; the Cmax are, respectively, 155 +/- 82 micrograms . 1(-1) and 133 +/- 104 micrograms . 1(-1). The AUC are 443 +/- 156 micrograms . 1(-1) h with the tablets and 315 +/- 178 micrograms . 1(-1) h with the solution. The short elimination phases, 1.43 +/- 0.80 h with the tablets and 1.55 +/- 0.78 h with the solution should be taken into account during chronic administration.

Administration, Oral↗
PubMed1983

The pharmacokinetics and availability of niflumic acid in humans.

The pharmacokinetic parameters and relative availability of niflumic acid in two different pharmaceutical preparations were studied in 12 subjects after a single oral administration. Total plasma clearance averaged 45 ml/min, and the half-life of elimination approximately 2 h, giving a distribution volume of 0.12 l/kg on the average. The values of these pharmacokinetic parameters were in agreement with the general characteristics of this type of substance, a weak acid strongly bound to plasma proteins. Comparison of the systemic availability of the two oral forms showed no difference; they were probably close to 100%.

Absorption↗
PubMed1981

Quantitative determination of niflumic acid and its beta-morpholinoethyl ester in human plasma by gas-liquid chromatography.

Niflumic acid and its beta-morpholinoethyl ester are extracted from plasma with diethyl ether. After methylation with diazomethane the solution is evaporated to dryness and the residue dissolved in methanol before injection in the chromatographic column. Using a nitrogen-sensitive detector the method permits the determination of 100 ng of each compound in 1 ml of plasma. The coefficient of variation is 5.3% and 4.8% for the acid and the ester, respectively, at the 2-microgram level.

Chromatography, Gas↗