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Biomedical subjects

J Adir

Publications and source records attributed to J Adir.

17 recordsLinked to original sources
PubMed1990

Excretion of tolbutamide metabolites in young and old subjects.

Tolbutamide (1 g/70 kg) was administered as a single intravenous dose to 31 healthy, non-smoking, drug-free males between 23 and 87 years old and the total amounts of hydroxy and carboxytolbutamide excreted in 24 h were measured. There was a significant decrease in the urinary recovery of both metabolites with age. The reason for these findings is not known at the present time and may be associated with the decrease in creatinine clearance observed in these subjects or other changes in the pharmacokinetics of tolbutamide which are currently being investigated.

Adult↗
PubMed1990

Effect of experimental hyperthyroidism on atropine pharmacokinetics in sheep.

Atropine sulfate (0.02 mg/kg, i.m.) was administered to normal sheep and to sheep with experimentally induced hyperthyroidism. Serum and urine concentrations of atropine measured by radioimmunoassay were monitored over an 8-h period. The time to reach maximum serum concentration was similar in both hyperthyroid and normal sheep. A comparison between normal and hyperthyroid sheep indicated that the atropine absorption rate was not changed, but its rate of elimination was significantly greater in hyperthyroid sheep (p less than 0.01). Hyperthyroidism resulted in significant decreases in atropine (p less than 0.05), MRT (p less than 0.01), AUC (p less than 0.01) and an increase in C1/F (p less than 0.01) when compared to atropine kinetics of normal sheep.

Animals↗
PubMed1987

Unusual absorption profile of phenytoin in a massive overdose case.

The pharmacokinetics of phenytoin was evaluated in a nonepileptic adult man after the ingestion of an undetermined amount of the drug following an apparent suicide attempt. A serum phenytoin concentration of 45 micrograms/mL was observed on admission 12 hours after ingestion. Phenytoin concentrations steadily increased, reached a maximum of 114 micrograms/mL four days later, then fluctuated at about 100 micrograms/mL for a week, and slowly declined to undetectable levels within the following week. At 96.5 micrograms/mL, the unbound serum concentration was 2.5 times that observed in therapeutic drug concentrations. Computer fitting of the data indicated that the Michaelis-Menten constants, apparent volume of distribution, and renal clearance of phenytoin were consistent with those parameters reported after therapeutic doses. However, phenytoin absorption was best described by parallel first- and zero-order rate processes, with the latter proceeding for as long as two weeks following drug ingestion. This protracted absorption appears to be a result of the presence of a large concretion of phenytoin in the gastrointestinal tract, having a slow disintegration and dissolution attributable to the limited solubility of the drug in the gastrointestinal tract and to the patient's diminished intestinal motility.

Adolescent↗
PubMed1987

Comparative efficacy and safety of immediate-release and controlled-release hydralazine in black hypertensive patients.

Twenty-nine black hypertensive patients were randomized to treatment with controlled-release hydralazine capsules administered BID or QD, or immediate-release hydralazine tablets administered TID, for at least four weeks in a double-blind, parallel study. Hydralazine was begun after a two-week to four-week period in which blood pressure was not adequately controlled with diuretics alone. Each patient initially received 75 mg/day of the assigned drug. The dosage could be increased to 150 or 300 mg/day at weekly intervals if sitting diastolic blood pressure was not adequately controlled (greater than 90 mmHg). A beta-blocker (80 mg/day of nadolol) was added only for patients who had beta-blocker-responsive adverse effects that could not be controlled otherwise. Nine patients were considered unevaluable because of protocol violations or withdrawal from the study before completion of four weeks of treatment, primarily because of adverse effects. Twenty patients were included in the efficacy evaluation. Controlled-release hydralazine BID produced statistically significant mean falls from baseline in sitting diastolic blood pressure and in standing systolic blood pressure and an almost significant drop in standing diastolic blood pressure. Although the other two treatment groups also had substantial falls in all blood pressure measurements, the changes from baseline were not statistically significant. No significant difference in response was noted between patients who received a beta-blocker and those who did not. There were no statistically significant differences among the three treatment groups in incidence and severity of adverse effects or electrocardiographic abnormalities. A statistically, but not clinically, significant fall in hemoglobin, hematocrit, and red blood cell count was observed in all three treatment groups.

Adult↗
PubMed1985

Nomogram for bretylium dosing in renal impairment.

Bretylium (Bretylol), an antiarrhythmic agent, is currently being used in the prophylaxis and treatment of patients with life-threatening ventricular fibrillation and tachycardia not responsive to conventional therapy. Because bretylium has a delayed onset of action that commonly causes hypotension and may increase ventricular irritability, its use in patients (especially patients with renal impairment) must be exercised with caution. Our results show that the maximum plasma concentration (Cmax) observed at the end of bretylium infusion, when normalized to the dose, increases significantly as renal function diminishes. Significant reductions in renal and total body clearance of bretylium have been observed in patients with renal insufficiency. In order to minimize the risk of potential toxicity following multiple dosing in such patients, dosage adjustments are necessary. Based on correlations developed between the total body clearance of bretylium and renal function, we present a nomogram herein that can be effectively used for adjusting the dosage of bretylium in patients with renal impairment.

Adult↗
PubMed1976

Disposition of nicotine in the rat after intravenous administration.

The pharmacokinetics of 14C-labeled nicotine were studied in male Fischer-344 rats following the i.v. administration of a single 0.8 mg/kg dose. Serial blood samples were collected and the nicotine in plasma was separated from its metabolites by TLC. The levels of radioactivity corresponding to nicotine, cotinine, and polar metabolites remaining at the origin of the chromatogram were determined by liquid scintillation counting. Plasma nicotine concentration was characterized by a biexponential decay with a mean biologic half-life (t1/2) of 0.96 hrs, a large apparent volume of distribution (5.67 L/kg) and total body clearance (4.04 L/hr/kg). Maximum plasma concentration of cotinine was reached within 1 1/2 hrs post-nicotine administration, followed by a monoexponential decline with a mean t1/2 of 6.4 hrs. The plasma concentrations of origin activity rose to maximum levels within 30 minutes and declined slowly in a biexponential fashion with a mean t1/2 of 23.2 hrs. It appears, therefore, that while nicotine is rapidly eliminated, its metabolites persist in the plasma a long time after its administration.

Animals↗
PubMed1975

Enterohepatic circulation of tetracycline in rats.

The absorption of tetracycline hydrochloride excreted in the bile of rats was evaluated using the insitu intestinal preparation. For comparative purposes, the absorption of the drug from an aqueous solution having the same pH as that of the bile was also determined. After 4 hr, the amounts of tetracycline absorbed from the bile and aqueous solutions were 72.92 and 77.34%, respectively. There was no significant difference in the amount of drug accumulated in the gut tissue. The disappearance of the drug from the intestinal lumen was biexponential, and the kinetic parameters appeared to be similar. It was concluded that tetracycline excreted in the bile is readily absorbed from the rat intestine. Accordingly, biliary excretion does not seem to account for a significant elimination of this antibiotic from the body.

Animals↗
PubMedDate not supplied

Pharmacolinetics of fluorocarbon 11 and 12 in dogs and humans.

Blood levels and exhalation bag contents of FC-11 and FC-12 from dogs and humans were used to elucidate the pharmacokinetic model describing the time-course of these agents. The derived pharmacokinetic parameters were in good agreement with the physicochemical properties of these substances. The model was used to estimate the percentage of dose absorbed, which averaged 77 per cent for FC-11 and 55 per cent for FC-12, and to predict the level of FC-11 and FC-12 under a variety of conditions simulating both short- and long-term exposure to the maximum allowable concentrations of these agents. With similar doses, an 8-hour continuous exposure was estimated to produce levels of FC-11 and FC-12 that are much lower than the corresponding levels reported to induce cardiac sensitization in dogs.

Animals↗
PubMedDate not supplied

Effect of dose on the pharmacokinetics of intravenous nicotine in the rat.

The pharmacokinetics of [methyl-14C]nicotine were evaluated in male Fischer-344 rats following the iv injection of 0.08-, 0.4-, or 0.8-mg/kg doses. Independent of dose, the concentration of nicotine declined biexponentially with a mean half-life ranging from 0.92 to 1.10 hr. However, the total plasma clearance of nicotine increased (p less than 0.05) from a mean value of 2.53 liter/hr-kg at the 0.08 mg/kg dose to mean values of 3.88 and 4.04 at the 0.4- and 0.8-mg/kg doses, respectively. There were no dose-related differences in the half-life of formation of the major metabolite, cotinine (range 0.33-0.46 hr) or the half-life of its elimination (range 5.39-6.63 hr). However, the areas under the cotinine plasma concentration-time curves did not increase proportionately with the dose of nicotine, indicating that the dose-related increase in the total plasma clearance of nicotine is not due to an increase in its biotransformation to cotinine. Similar conclusions were obtained with regard to the disposition kinetics of other polar metabolites of nicotine. The urinary excretions of nicotine and its metabolites were dose-independent.

Animals↗