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Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 487 records · Page 27Linked to original sources
PubMed1975

Effect of carbonated beverages and of an antiemetic containing carbohydrate and phosphoric acid on riboflavin bioavailability and salicylamide biotransformation in humans.

Two carbohydrate-phosphoric acid solutions, one a widely used beverage (Solution C) and the other a pharmaceutical product used as an antiemetic (Solution E), administered together with riboflavin-5'-phosphate or salicylamide to healthy human adults, significantly increased the bioavailability of riboflavin and appreciably altered the metabolic fate of salicylamide (increased conversion to the sulfate and decreased formation of the glucuronide). A beverage containing phosphoric acid but no carbohydrates (Solution T) also increased the bioavailability of riboflavin but not as much as Solution C. These effects are attributed to a decrease of the gastric emptying rate caused by carbohydrates and phosphoric acid, consistent with the empirical use of Solution C syrup and Solution E as antinauseants and antiemetics. The results demonstrate also that the choice of beverage to be taken with medication can affect the bioavailability and/or metabolic fate of medicinals with saturable absorption and/or biotransformation characteristics.

Adult↗
PubMed1975

Comparative pharmacokinetics of coumarin anticoagulants. XIV: relationship between protein binding, distribution, and elimination kinetics of warfarin in rats.

The relationships between the protein binding, distribution in the body, and kinetics of elimination of warfarin were studied. Individual rats eliminated warfarin by apparent first-order kinetics, with a biological half-life of 5.9-41 hr and a total plasma clearance of 2.4-22 ml kg(-1) hr(-1). There is a strong positive correlation between the apparent volume of distribution (Vd) and the elimination rate constant (kel). There was no apparent concentration dependance of warfarin binding to serum proteins over a wide concentration range, but there were pronounced intersubject variations in protein binding, with the free fraction of drug (f) in serum ranging from 0.172 x 10(-2) to 1.53 x 10(-2). There are strong positive correlations between f and kel, f and Vd, and f and the kidney-serum concentration ratio of warfarin. Consistent with theory, there is an excellent positive linear correlation between f and total plasma clearance of the drug. The intersubject variation in f is not related to variations in serum albumin or total protein concentration. There is a strong correlation between values of f for serum and liver homogenate in individual animals, consistent with the lack of correlation between f in serum and the liver-serum concentration ratio of warfarin. These results show that the pronounced intersubject variation in the elimination of warfarin observed in this investigation was related to interindividual differences in plasma protein binding of the drug. The differences in protein binding cannot be ascribed to differences in plasma protein concentrations and may reflect configurational differences of proteins or the presence of an endogenous displacing agent at different concentrations.

Animals↗
PubMed1975

Inhibition of drug metabolism by hydroxylated metabolites: cross-inhibition and specificity.

Inhibition of drug metabolism was studied in adult male Sprague-Dawley rats. A hydroxylated metabolite of phenylbutazone (oxyphenbutazone) inhibited the elimination of phenytoin, which is metabolized by oxidative pathways. The biotransformation of a relatively polar and only slightly plasma protein-bound drug, antipyrine, was subject to product inhibition by a hydroxylated metabolite, 4-hydroxyantipyrine. Neither oxyphenbutazone nor 4-hydroxyantipyrine measurably affected the elimination kinetics or metabolic fate of a drug (sulfanilamide) that is not metabolized by oxidative pathways.

Animals↗
PubMed1975

Comparative pharmacokinetics of coumarin anticoagulants XV: relationship between pharmacokinetics of dicumarol and warfarin in rats.

The distribution, elimination, and anticoagulant effect of dicumarol and warfarin were determined in adult males rats following intravenous injection of single doses of these drugs in crossover experiments. The biological half-life of dicumarol ranged from 5 to 28 hr; that of warfarin ranged from 9 to 30 hr. There was a statistically significant correlation between the following pharmacokinetic characteristics of dicumarol and warfarin in individual animals: biological half-life, apparent volume of distribution, total plasma clearance, and concentration in plasma eliciting one-half the maximum anticoagulant effect (effective concentration). The mean ratio of the respective biological half-lives (warfarin/dicumarol) was 1.42, and that of the apparent volumes of distribution was 1.50. The ratio of the effective plasma concentrations (dicumarol/warfarin) was correlated negatively with the half-life of dicumarol and positively with the ratio of the half-life values (warfarin/dicumarol) in individual animals. Additional studies with serum samples from other rats showed pronounced interindividual differences in the serum protein binding of both dicumarol and warfarin and a strong correlation between the protein binding of these two drugs in serum of individual animals. The results of this study, together with the results of previous studies in this series, indicate that serum protein binding is the major determinant of interindividual differences in the pharmacokinetics of dicumarol and warfarin in rats under these experimental conditions.

Animals↗
PubMed1975

Time course and dose dependence of antacid effect on urine pH.

Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15 ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5-ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30 ml four times a day increased urine pH by approximately the same magnitude as the 15-ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing.

Adult↗
PubMed1975

Pharmacokinetic analysis of the effect of theophylline on pulmonary function in asthmatic children.

Previously published data of plasma concentrations and pharmacologic effects obtained after rapid intravenous injection and during constant rate intravenous infusion of theophylline in asthmatic children were analyzed pharmacokinetically to determine the relationship between effect on pulmonary function (improvement of forced expiratory volume in the first second) and drug level. The pharmacokinetics of distribution and elimination of theophylline are well described by a linear two-compartment open model consisting of a central and a tissue compartment. There is an essentially linear correlation between the intensity of effect and the logarithm of the amount of drug in the tissue compartment. This correlation exists both with decreasing and increasing drug concentrations, i.e., after intravenous injection and during intravenous infusion of theophylline.

Adolescent↗
PubMed1975

Effect of bilirubin on the distribution, elimination and anticoagulant action of dicumarol in Gunn rats-1-2 (38547).

Jaundiced Gunn rats were found to have a significantly larger apparent volume of distribution and higher rate constant for elimination of dicumarol than their nonjaundiced littermates. Anticoagulant effect-log plasma dicumarol concentration lines were parallel in the two groups of animals, with the line for the jaundiced rats shifted to a lower concentration range. In vitro studies showed that bilirubin can displace dicumarol from serum protein binding sites. There are indications of a genetic influence on the distribution and anticoagulant effect of dicumarol in Gunn rats.

Animals↗
PubMed1975

Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion.

The purpose of this study was to determine if certain physiologic parameters (plasma bilirubin concentration and urinary excretion rate of D-glucaric acid) can be used to predict a newborn infant's ability to eliminate a phenolic drug, and particularly to predict the ability to conjugate that drug with glucuronic acid. Tweleve healthy 2- to 3-day-old full-term infants with plasma bilirubin concentrations of 1.0 to 11.6 mg/100 ml and D-glucaric acid excretion rates of 0.131 to 0.345 mg/kg/day received a single oral dose of acetaminophen, 12 mg/kg. Urine was collected serially for 48 hours and analyzed for acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, and D-glucaric acid. The biologic half-life of acetaminophen was 3.5 plus or minus 0.85 hours (average plus or minus SD) as compared to average values of 1.9 to 2.2 hours observed in five reported studies on a total of 39 adults. The rate constant for acetaminophen glucuronide formation in neonates was considerably smaller, on the average, than in adults but the average rate constant for acetaminophen sulfate formation was somewhat larger than in adults. There is not statistically significant colucaric acid excretion. The results of this study suggest that the limited ability of neonates to conjugate phenolic drugs with glucuronic acid is compensated to a degree by a well-developed capability for sulfate conjugation.

Acetaminophen↗
PubMed1975

Inhibition by ice cream of the antidotal efficacy of activated charcoal.

A study was conducted to determine if ice cream and sherbet interfered with the adsorption of aspirin onto activated charcoal both in vivo and in vitro. An aqueous suspension of 20 g activated charcoal decreased the absorption of 1 g aspirin by 65%; the same dose of activated charcoal with 50 g of ice cream reduced aspirin absorption by only 42% under otherwise identical conditions. In vitro tests showed that different ice creams and sherbet decrease the adsoprtion of aspirin onto activated charcoal. Thus, although ice cream is useful for preparing palatable suspensions of activated charcoal, it decreases appreciably the antidotal efficacy of the adsorbent.

Adult↗
PubMed1975

Effect of plasma protein binding on the anticoagulant action of warfarin in rats.

The relationships between the anticoagulant effect and the concentrations of free and total (sum of free and protein-bound) warfarin in plasma were determined in rats following intravenous administration of single doses of racemic warfarin or S(-)-warfarin. The concentration of total warfarin required to elicit a defined anticoagulant effect varied widely between animals while the concentration of free warfarin showed much less variation. This indicates that the anticoagulant effect of warfarin is a function of its free concentration in plasma.

Animals↗
PubMed1975

[Resistance test to streptokinase. Its value in the establishing of a thrombolytic treatment using this enzyme].

The reckoning of the rate of serous anti-streptokinase (ASK) evidenced that 8 p. 100 of the test-sample presented a distinct resistance to Streptokinase (SK), and that this percentage could be more important under certain pathological circumstances. On account of this fact and also because SK injectable preparations may offer a variation in activity, the writers advocate a "preliminary control in vitro" by means of the resistance test to streptokinase that enables one to make sure, for each patient, of the biological efficacy of the drug and to specify the starting posology.

Aged↗