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Biomedical subjects

A Leroy

Publications and source records attributed to A Leroy.

At least 109 records · Page 6Linked to original sources
PubMed1981

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

The pharmacokinetics of moxalactam were investigated in five subjects with normal renal function and 21 uremic patients. Normal subjects were given intravenous doses of 7.5 and 15 mg of the drug per kg as bolus injections (1 min) and 30 mg of the drug per kg as a 20-min infusion. Pharmacokinetic data, calculated by using a two-compartment open body model, were similar for the three intravenous doses: the t 1/2 alpha value was within 0.12 to 0.20 h, the t 1/2 beta value was 1.98 to 2.05 h, the central distribution volume (Vc) was 3.81 to 7.04 liters/1.73 m2, and the apparent volume of distribution at steady state (Vdss) was 9.12 to 13.36 liters/1.73 m2, i.e., 13.7 to 20.2% of the body weight. From 82.0 to 97.7% of the dose was recovered, in unchanged form, in urine during 24 h. After a single intramuscular dose of 15 mg/kg in the same subjects with normal renal function, the mean peak serum levels, occurring at 0.95 +/- 0.37 h, were 48.28 +/- 11.81 microgram/ml, the t 1/2 beta value was 2.22 +/- 0.16 h, the renal clearance (CR) was 87.5 +/- 9.4 ml/min per 1.73 m2, and 96.9 +/- 12.7% of the injected dose was found in 24-h urine. Pharmacokinetic data were similar for the two routes of administration. In uremic patients, the t 1/2 beta increased according to the severity of renal failure; it was 4.83 h in patients with creatinine clearances (Ccr) within 30 to 60 ml/min per 1.73 m2, 8.42 h for Ccr values within 10 to 30 ml/min, and 18.95 h in hemodialysis patients. During a 4- to 6-h dialysis session, the t 1/2 beta value was 3.65 h and 51% of the drug was removed by dialysis. The apparent volume of distribution at steady state increased in patients with Ccr values below 10 ml/min; serum and renal clearances decreased in uremic patients, and the nonrenal clearances remained constant in all these patients. From these pharmacokinetic results, linear relationships were found between the kinetic data and the biological parameters of the glomerular filtration rate. Dosage schedules were established, adapted to the degree of renal impairment.

Adult↗
PubMed1981

Pharmacokinetics of azlocillin in healthy subjects.

The pharmacokinetics of azlocillin were investigated in six healthy subjects with normal renal function. 40.4 to 69.6% of the injected dose was recovered, estimated as unchanged form, in urine during 24 h. After intravenous bolus injection of 15 and 30 mg/kg doses, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T1/2 alpha) was 0.11-0.12 h and the mean elimination serum half-life (T1/2 beta) was 0.79-0.89 h. The volume of the central compartment (Vc) was 7.36-8.01 1/1.73 m2 and the apparent volume of distribution (Vdss) was 14.12-14.32 1/1.73 m2. The mean T1/2 beta after a 30 min i.v. infusion of 80 mg/kg to the same healthy subjects was 1.10 h. Serum clearances (Cs) for 15, 30 and 80 mg/kg were 251.1, 214.0 and 152.9 ml/min/1.73 m2 and renal clearance (Cr) were 99.7, 145.2 and 94.1 ml/min/1.73 m2, respectively. Azlocillin pharmacokinetics were found to be dose dependent. Administration of probenecid increased the terminal serum half-life and the total area under the serum azlocillin concentration-time curve and decreased renal clearance, indicating that azlocillin is eliminated by both glomerular filtration and tubular secretion.

Adult↗
PubMed1980

Cis-Dichlorodiammine platinum and adriamycin therapy for advanced gynecological and genitourinary neoplasms.

Cis-Dichlorodiammine platinum (DDP) 75 mg/m2 on days 1 and 8 and Adriamycin (ADR) 60 mg/m2 on day 1 were used in 31 patients with advanced gynecological and genitourinary neoplasms. The DDP was given by 6 hours intravenous infusion with 2 liters of 5% Dextrose and 0.5 normal saline using Mannitol and/or furosemide diuresis. Courses were repeated every 21 to 28 days. Responses were seen in 7 of 8 patients with germinal cell neoplasms (5 complete, 2 partial) with a median duration of eight months. A partial response was obtained in 3 of 7 patients with bladder carcinoma with a median duration of three months. There were four partial responses obtained in 9 patients with ovarian carcinoma with a median duration of five months. Toxicities included nausea and vomiting in all 31 patients, nephrotoxicity (serum creatinine > 2 g/100 ml) in patients, tinnitus and/or high frequency hearing loss in 10 patients, and neurotoxicity (peripheral neuropathy, normal pressure hydrocephalus, papilledema) in 8 patients. Severe leukopenia (WBC < 2000/cu mm) and thrombocytopenia (< 100,000/cu mm) occurred in 25% and 45% of evaluable courses, respectively and necessitated dosage reduction in all and delay of therapy in some patients. Peak plasma Pt levels were 2.61 +/- .18 microgram/cc on day 1 and 3.52 +/- .39 microgram/cc on day 8 with a longer terminal half-life on day 8 (252 hours) compared to day 1 (156 hours). Peak plasma ADR levels ranged from .53 to 1.67 N moles/cc with an average terminal half-life of 22.8 hours. This agrees with values of ADR when given alone. This dose and schedule of DDP-ADR is active against advanced gynecological and genitourinary neoplasms, but the amount of toxicity seen indicates that modifications will have to be made.

Adolescent↗
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

Cefoxitin concentrations in the cerebrospinal fluids of patients with meningitis.

The concentrations of cefoxitin in serum and cerebrospinal fluid (CSF) were measured simultaneously in three groups of patients, 12 with aseptic meningitis (group 1) and 17 and 14 with bacterial meningitis (groups 2 and 3). The patients in group 1 received a single intravenous dose of 2 g of cefoxitin without other antimicrobial therapy. In addition to conventional doses of ampicillin or benzyl penicillin, patients in groups 2 and 3 received repeated infusions of 2 g of cefoxitin every 4 h for the first 3 or 4 days of the study and again on day 10. Additionally, group 3 received probenecid in a loading dose of 1 g followed by 0.5 g every 6 or 8 h. Concentrations of cefoxitin in CSF and serum were determined 1 or 2 h after infusion in group 2 and 2 h after infusion in group 3. The concentrations of cefoxitin in CSF did not reach detectable levels (1.56 microgram/ml) in 11 of the 12 patients in group 1. A level of 2.8 microgram of cefoxitin per ml of CSF was found, with an accompanying level of 30 microgram/ml of serum, in patient 12. In the group 2 patients with bacterial meningitis, the mean CSF concentrations were 3.3, 4.7, and 2.9 microgram/ ml on days 1, 3, and 10 of treatment, with simultaneous serum levels of 8, 9, and 8 microgram/ml. At similar times periods, the mean levels of cefoxitin in group 3 patients (with concomitant probenecid) were 8.6, 12.3, and 4.3 microgram/ml of CSF and 57, 35, 27 microgram/ml of serum.

Adolescent↗
PubMed1979

Pharmacokinetics of amoxicillin: Dosage nomogram for patients with impaired renal function.

Amoxicillin pharmacokinetics after intravenous administration were studied in patients with normal renal function, with impaired renal function, and during hemodialysis. The average urinary recovery was 68% in patients with normal renal function. Serum half-life was highly correlated (r = 0.967) with creatinine clearance corrected for body weight. Expected half-life was 71 min for a corrected creatinine clearance of 100 ml/min per 70 kg and 16 h in the anephric patient. Average amoxicillin half-life on hemodialysis was 3.6 h. We present a dosage nomogram for making appropriate adjustments to loading dose based on patient weight and maintenance dose based on corrected creatinine clearance.

Amoxicillin↗
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

Pharmacokinetics of netilmicin in the presence of normal or impaired renal function.

A pharmacokinetic study of netilmicin was conducted in 12 healthy subjects and 24 subjects with chronic renal failure. After intramuscular administrations of 2 and 3 mg of netilmicin per kg in normal subjects, the mean peak serum concentrations were 5.46 and 8.83 mug/ml, respectively. After intravenous infusions of identical doses, the mean maximum serum levels, occurring at the end of the infusion, were 11.79 and 15.75 mug/ml, respectively. The pharmacokinetic data were very similar via the two routes of administration and for the two doses. The elimination half-life was 2.20 h, and 80 to 90% of the injected dose was recovered in urine during the first 24 h. After intramuscular administration of 2 mg/kg in subjects with chronic renal impairment, the elimination half-life increased to 29.48 h, and urinary elimination was inversely related to the degree of impairment. A study was conducted throughout hemodialysis sessions: serum concentrations decreased by 63.3%. The linear relationships between the elimination rate constant and creatinine clearance and the elimination half-life and serum creatinine allowed us to establish dosage schedules according to the degree of renal failure.

Adult↗
PubMed1978

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

Since aminoglycosides are antibiotics almost exclusively eliminated by the kidneys, their pharmacokinetic study in normal subjects and in uraemic patients is essential to establish dosage schedules adapted to various degrees of renal impairment. Many studies have been recently reported, particularly with regard to the newly developed desoxystreptamine aminoglycoside antibiotics. The present paper is a compilation of our own results and a review of the literature concerning Streptomycin, Kanamycin and its semi-synthetic derivation, Amikacin or BB-K8, Gentamicin, Tobramycin, Lividomycin, Sisomicin and its semi-synthetic derivation, Netilmicin.

Aminoglycosides↗
PubMed1978

[Interhemispheric disconnection syndrome with diagonistic dyspraxia in the course of Marchiafava-Bignami disease].

The probable diagnosis of Marchiafava-Bignami disease was made in a chronic alcoholic patient because of the rapid onset of signs of inter-hemisphere disconnection. These inclused left visual and tactile anomia, difficulty of a limb to imitate postures presented in the contralateral visual half-field, constructional apraxia of the right hand, agraphia of the left hand, left auditive extinction in the dichotic test, difficulty in responses of the left limbs to verbal orders, which the authors propose to name left "aphasic apraxia" and a bimanual asynergia, sometimes presenting an aspect of diagonistic dyspraxia. These symptoms clearly show the competence of the left hemisphere for verbal tasks, or more generally, those of an imaginary or conceptual nature, and that of the right hemisphere for visiopatial tasks, or more generally, those required by concrete situations.

Agraphia↗
PubMed1977

[Cephalosporins].

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Cephalosporins↗