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Biomedical subjects

M Godin

Publications and source records attributed to M Godin.

At least 127 records · Page 7Linked to original sources
PubMed1980

Pharmacokinetics of azlocillin in subjects with normal and impaired renal function.

The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a single dose of 30 mg/kg in normal subjects, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T(1/2alpha)) was 0.11 h, and the mean elimination serum half-life (T(1/2beta)) was 0.89 h. The volume of the central compartment (V(C)) was 7.36 liters/1.73 m(2), and the apparent volume of distribution (V(dss)) was 14.15 liters/1.73 m(2), i.e., 21.9% of body weight. The T(1/2beta) after a 30-min intravenous infusion of 80 mg/kg to the same healthy subjects was 1.11 h. Serum clearances (C(S)) for the 30- and 80-mg/kg doses were 215.0 and 152.9 ml/min per 1.73 m(2). The mean renal clearances (C(R)) were 145.2 and 94.1 ml/min per 1.73 m(2) for the respective doses. Between 61.8 and 69.6% of the injected dose was recovered in urine during the first 24 h. The elimination half-life in subjects with chronic renal impairment increased with the degree of renal insufficiency. After a 30-min intravenous infusion of 80 mg/kg the T(1/2beta) values were 2.03, 4.01, and 5.66 h with creatinine clearances (C(cr)) within 30 to 50, 10 to 30, and <10 ml/min per 1.73 m(2), respectively. Urinary elimination was inversely related to the degree of renal impairment. In four patients out of and on a 6-h hemodialysis session mean elimination half-life values were 6.53 and 2.81 h, respectively. The fraction of drug removed by dialysis was 45.8%. The linear relationships between the elimination of half-life (T(1/2beta)) and serum creatinine and the elimination rate constant (beta) and creatinine clearance (C(cr)) provided a basis for adjustment of dosage in renal failure.

Adult↗
PubMed1980

[Functional, histological, ultrastructural and biochemical study of rat kidney treated with fosfomycin and gentamycin, administered separately or together].

Wistar rats received by intraperitoneal injection for 8 days different doses of Fosfomycin, a new antibiotic. No renal pathological changes are seen under light microscopy after these treatments. Ultrastructural study reveal an intact cellular structure of the proximal tubule. Fosfomycin induces no change in the lysosomal structural latency and enzymatic study show no change in the activities of our hydrolases (alanine-aminopeptidase, alpha-galactosidase, N-acetyl-beta-D-glucosaminidase and sphingomyelinase), after treatment by 100 and 500 mg/kg Fosfomycin. At 1000 mg/kg, Fosfomycin induces an inhibition in enzymatic activities of the four hydrolases. Fosfomycin does not modify the activity of Gentamicin on the proximal tubular cell and induces neither protection nor potentialization of its nephrotoxic effect.

Acetylglucosaminidase↗
PubMed1980

[Pharmacokinetic study of guanfacine in patients with renal insufficiency and in patients under chronic dialysis (author's transl)].

The pharmacokinetics of guanfacine (GF, antihypertensive agent with central action) were studied in five patients with renal insufficiency (CCr less than 30 ml/min) after oral administration of a single 4 mg dose. GF was rapidly absorbed, the peak plasma levels (13.28 +/- 1.58 ng/ml) being reached within two hours. The plasma level decreased with a bi-exponential pattern, with a t 1/2 of the beta phase of 24.4 +/- 3.2 h. The plasma clearance was 212 +/- 40 ml/min and the renal clearance 13.9 +/- 5.2 ml/min. The comparison of these results with those observed in hypertensive patients with a normal renal function demonstrates a slower elimination (t 1/2 beta in the reference group of 16.7 h) and a decrease of the total and renal clearances (445 +/- 29 ml/min and 144 +/- 6 ml/min respectively of the reference group) which directly correlated with the decrease of the CCr. The volume of distribution, however, does not seem to be modified. In 5 other patients under chronic dialysis treated with GF for several months, the cumulation was not more improvement than in the chronic renal insufficient group. The dialysis did not appear to interfere with the elimination kinetics of the drug.

Antihypertensive Agents↗
PubMed1979

[Hypouricaemia (author's transl)].

Hypouricaemia (blood level blow 2 mg/100 ml or 12 mumol/100 ml) is rarely observed, i.e., in less than 1% of hospitalized patients. Hypouricaemia can be induced by any of three mechanisms: a decrease in uric acid synthesis due to deficient xanthine oxydase (e.g., hereditary xanthinuria, severe liver disease, treatment with allopurinol); increased uricolysis due to drug therapy; increased urinary excretion of uric acid. This increased urinary excretion is due to abnormal uric acid transport in the proximal tubule. It is sometimes observed alone (primary hereditary anomaly of tubular uric acid transport, severe liver disease or neoplasia, drugs, or contrast media). It can also be observed in association with other proximal tubular anomalies, constituting a Fanconi syndrom. Among observations of hypouricaemia, 50% result from drug therapy and approximately 30% are secondary to liver diseases or neoplasia. It has no special clinical consequence. Nevertheless, the observation of hypouricaemia in a patient should indicate the possibility of drug intoxication or an underlying disease, in particular neoplasia. Measurement of uric acid clearance is a simple method of determining the mechanism responsible and of guiding diagnosis.

Allopurinol↗
PubMed1979

Pharmacokinetics of cefadroxil in normal subjects and in patients with renal insufficiency.

Pharmacokinetics of cefadroxil, a new orally semisynthetic cephalosporin, was studied in 5 subjects with normal renal function and in 20 patients with varying degrees of renal insufficiency. All subjects received 1,000 mg per os in a single dose and the elimination phase was studied. In healthy subjects, elimination half-life (T1/2) was 1.39 +/- 0.06 h. Apparent volume of distribution was 0.305 liters/kg and area under the serum concentration versus time curve AUC was 82.94 +/- 19.98 microgram . h/ml. Peak level averaged 25.72 +/- 4.68 microgram . ml-1 and occurred at 1.20 +/- 0.45 h postingestion. 93.0 +/- 3.6% of the dose was recovered in urine during the first 24 h. Renal and serum clearance averaged 166.7 and 172.4 ml . min-1/1.73 m2, respectively. In patients with renal insufficiency, T1/2 increased to 25.49 h in severe chronic renal failure. Renal impairment did not significantly modify volume of distribution. During a 6- to 8-hour hemodialysis session, antibiotic serum concentrations decreased by 75.4 +/- 5.6%. Dosage schedules could be suggested on the basis of these pharmacokinetic results.

Administration, Oral↗
PubMed1978

[Renal function and histologic studies in rats treated by floctafenin (author's transl)].

The nephrotoxic action of floctafenin has been studied in rats. When administered orally at 20 or 50 mg/kg/day for 20 or 50 days, this analgesic agent had no effect on the renal function, either in intact rats or in animal with reduced renal parenchyma. There is no histological change in the kidneys of the treated animals except some focal dilatations of the distal tubules. The tubular alterations were more important in treated and untreated rats with nephronic reduction. The whole body autoradiographic studies of rats treated with 14C floctafenin showed that liver and kidney accumulate radioactivity, and that the intake of radiolabeled compounds is twice higher in renal cortex than in medulla. This study suggests that the toxicity of floctafenin for the rat kidney is very low or none.

Animals↗
PubMed1978

[Prazosine: a new vasodilator used for treatment of hypertension (author's transl)].

Prazosine, a derivative of quinazoline, acts by relaxing the smooth vascular muscles and blocking postsynaptic alpha-adrenoreceptors. A special protocol was used to treat arterial hypertension in 21 subjects. A small dose (0.5 mg) was given the first day to avoid orthostatic hypotension, then 0.5 mg x 3 on days 2, 3 and 4, followed by 1 mg x 3 on subsequent days. Dosage can be progressively increased up to 30 mg/day. During the first 36 days of treatment, prazosine was given alone. A significant drop in systolic and diastolic arterial pressure was observed in the reclining subject. The effect on orthostatic pressures were nevertheless significantly lower than before initiating treatment. Prazosine induces only a slight increase plasma renin activity. In 9 patients the use of prazosine alone at 3 to 6 mg per day produced not only a drop in arterial pressure but its normalization. In 5 other patients, the administration of prazosine associated with a beta-blocker, acebutolol, induced normalization of arterial pressure. The association of prazosine with a thiazide diuretic was not considered successful. In 5 patients, treatment was interrupted with the appearance of coronary insufficiency, orthostatic hypotension and frequent headaches. Minor side-effects observed in 8 others patients did not require interruption of treatment. Based on the above results, it can be stated that prazosine is an efficient new peripheral vasodilator with good patient tolerance for the treatment of arterial hypertension.

Acebutolol↗