PubMed Health⌕ Search

Biomedical subjects

A Yacobi

Publications and source records attributed to A Yacobi.

At least 19 recordsLinked to original sources
PubMed1991

Pharmacokinetic principles in the design of immediate-release components in sustained-release formulations with zero-order release characteristics.

The potential advantages and disadvantages of incorporating an immediate-release (IR) component in sustained-release formulations with zero-order release characteristics (SR) are discussed. The dose of the IR component for SR doses other than the first one (DIS) should be less than that for the first SR dose (DI). Multiple dosing of an SR formulation with an IR component of dose DI may lead to unnecessary accumulation and fluctuation of plasma drug concentrations. An innovative and practical method for estimating the DI and DIS doses of this IR component is also presented.

Chemistry, Pharmaceutical↗
PubMed1979

Effect of serum protein binding on sulfisoxazole distribution, metabolism, and excretion in rats.

This investigation determined the effect of serum protein binding on the kinetics of sulfisoxazole distribution, metabolism, and excretion. Adult rats, whose serum free fraction of sulfisoxazole (at a total concentration of 81 +/- 6 micrograms/ml) was 0.05-0.24, received a rapid intravenous injection of 20 mg/kg. Sulfisoxazole concentrations in plasma declined biexponentially with time. There were pronounced and reproducible interindividual differences in the total, metabolic, and renal sulfisoxazole clearances, each positively correlated with the serum free fraction of sulfisoxazole. The renal sulfisoxazole clearance had a component unaffected by serum protein binding. The apparent central compartment volume increased with an increasing serum free sulfisoxazole fraction, but the latter had not apparent effect on the first exponential term of the biexponential equation describing sulfisoxazole elimination kinetics in rats. Serum protein binding was a major determinant of intersubject differences in sulfisoxazole excretion and biotransformation kinetics.

Animals↗
PubMed1979

Urinary excretion of chlorpheniramine and pseudoephedrine in humans.

A specific high-pressure liquid chromatographic method for the determination of chlorpheniramine and pseudoephedrine in urine was developed and applied in a urinary excretion study of normal healthy subjects who received a sustained-release dosage form contianing 8 mgof chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride. Five subjects received one dose on Day 1, followed by multiple dosing every 12 hr for 7 days without ammonium chloride administration. Four subjects received one dose of the sustained-release dosage form together with ammonium chloride. Urine samples were collected during the 1st day and at steady state. The method is specific and simultaneously determines choorpheniramine, two metabolites (mono- and di-desmethylchlorpheniramine), pseudoephedrine, and norpseudoephedrine. The assay recovery was less than 97% (0.06-3 microgram/ml) for chlorpheniramine maleate and less than 98% (1.5-75 microgram/ml) for pseudoephedrine hydrochloride. Excretion of chlorpheniramine and its two metabolites in urine was enhanced after ammonium chloride administration. At steady state, a change in urine pH from 5.69 to 6.46 resulted in more than a 25% decrease in chlorpheniramine and monodesmethylchlorpheniramine excretion. In spite of expected changes in its biological half-life, the overall amount of unchanged pseudoephedrine excreted in urine was not affected by urine pH, presumably because it is primarily excreted in urine as intact drug.

Chlorpheniramine↗
PubMed1979

Effective plasma concentration of N-acetylprocainamide in rats.

Six groups of rats received saline or N-Acetylprocainamide (NAPA) 2--50 mg/kg, intraperitoneally. Thirty minutes later heart rates were measured and simultaneously a blood sample was withdrawn from each rat. There was a linear relationship between plasma concentrations and the administered doses, suggesting linear pharmacokinetics for NAPA. The heart rate was decreased significantly when the average NAPA plasma concentration was 16.8 microgram/ml, which is similar to that found in man.

Animals↗
PubMed1978

Comparison of in vitro dissolution and in vivo bioavailability of methaqualone tablets in humans.

Two methaqualone tablets that exhibited different in vitro dissolution rates were administered to 11 normal healthy male volunteers. Serial blood samples were withdrawn following administration of each tablet, and plasma methaqualone concentrations were determined by an established spectrophotofluormetric assay. Both tablets produced virtually identical plasma concentration versus time profiles in humans, and no statistically significant differences in either the rate or extent of drug absorbed were detected. The results indicate that there is no correlation between in vivo bioavailability and the modified NF in vitro dissolution test used.

Adult↗
PubMed1978

Simultaneous determination of pseudoephedrine and chlorpheniramine in pharmaceutical dosage forms.

A simple and sensitive high-pressure liquid chromatographic (HPLC) determination of pseudoephedrine and chlorpheniramine in a pharmaceutical dosage form is described. Quantities of 1.5 microgram of pseudoephedrine and 0.1 microgram of chlorpheniramine are sufficient to determine concentrations in an aqueous solution. Small volume samples, without any extraction procedures, can be treated for direct drug concentration measurement with a high-pressure liquid chromatograph. The stability-indicating property and the accuracy of this method are comparable to those of an established GLC method. The HPLC method can be applied directly and successfully for dissolution studies. The latter application eliminates the need for volume replacement or subsequent mathematical corrections.

Capsules↗
PubMed1977

Frequency distribution of free warfarin and free phenytoin fraction values in serum of healthy human adults.

The protein binding of racemic warfarin was determined in serum from 57 normal adults (27 men and 30 women). The free fraction of warfarin (total concentration, 0.8 mug/ml) ranged from 0.0050 to 0.0186 and was log-normally distributed. The frequency distribution differs from that in rats in which the serum free fraction values of warfarin are trimodally distributed. The protein binding of phenytoin was determined in serum from 39 of the subjects. The free fraction of phenytoin (total concentration, 15 mug/ml) ranged from 0.111 to 0.155 and was unimodally distributed. There was no apparent correlation between the extent of protein binding of warfarin and phenytoin in individual serum samples. The pronounced intersubject variation in serum free fraction of warfarin observed in consistent with our previous finding that serum protein binding is an important determinant of interindividual differences in the total clearance of warfarin in man. On the other hand, the relatively narrow distribution of free phenytoin fraction values suggests that differences in serum protein binding of phenytoin are not an important cause of the prounounced interindividual differences in the total clearance of phenytoin by subjects with normal renal function.

Adolescent↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXI: effect of plasma protein binding on distribution kinetics of warfarin in rats.

The purpose of this investigation was to determine the effect of plasma protein binding on the pharmacokinetic parameters for warfarin that are used conventionally to describe its distribution kinetics on the basis of the time course of plasma warfarin concentrations. Following rapid intravenous injection, warfarin concentrations in the plasma of 14 selected adult male rate declined triexponentially, with the terminal exponential phase starting at about 5 hr. The free fraction, f, of warfarin in the serum of individual animals ranged from 0.303 X 10(-2) to 2.89 X 10(-2). The parameters of the equation Ct = Pe-theta + Ae-alphat + Be-betat for plasma concentration Ct at time t were obtained from the experimental data by nonlinear least-squares computer fitting and varied markedly between animals. Strong and highly statistically significant positive correlations with f were obtained for P, B, and beta, but no significant correlation was found for A, theta, and alpha. Rate constants and apparent volumes for a three-compartment open mammillary model with elimination from the central compartment were calculated. No apparent correlation was found between f and the intercompartment distribution rate constants. However, strong positive correlations between f and the elimination rate constant, the volume of the central compartment, and the volume of distribution, V area, were observed. There also was a strong linear correlation between f ant total clearance. Excellent replication of the experimental data was obtained when the experiment were repeated in some animals after 2 weeks. A detailed analysis of practical pharmacokinetic problems associated with and revealed by such repeated experiments is presented.

Animals↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXIV: Effect of treatment with phenobarbital on serum protein binding of warfarin and dicumarol in rats.

Rats were treated with the enzyme inducer phenobarbital to determine if it would affect the serum protein binding of warfarin and dicumarol, possibly by changing the rate of formation or elimination of endogenous inhibitor(s). Daily administration of phenobarbital, 75 mg/kg, for 4 days increased relative liver size (a concomitant of enzyme induction) but had no apparent effect on the serum protein binding of warfarin and dicumarol.

Animals↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXV: Warfarin-ibuprofen interaction in rats.

The effect of ibuprofen on the pharmacokinetics and anticoagulant action of racemic warfarin was determined in a crossover study on male Sprague-Dawley rats. At average plasma concentrations of 24-83 mg/liter, ibuprofen decreased the biological half-life and increased the total clearance of warfarin. It also increased the anticoagulant effect produced by a given plasma concentration of total (free and protein-bound) warfarin. These effects of ibuprofen appear to be a consequence of its displacing effect on warfarin in plasma.

Animals↗
PubMed1977

Relationship between protein binding of bilirubin, salicylic acid, and sulfisoxazole in serum of unmedicated and phenobarbital-treated rats.

The relationship between the protein binding of bilirubin, salicylic acid, and sulfisoxazole in the serum of phenobarbital-treated and untreated rats was studied. The free fraction of bilirubin in serum varied about threefold between animals but was not related to the albumin concentration, the free fraction of salicylate, or the free fraction of sulfisoxazole. However, there was a strong positive correlation between the free fraction values of salicylate and sulfisoxazole. The free fraction value for each of these drugs showed a significant negative correlation with the serum albumin concentration. Treatment of the animals with phenobarbital had no apparent effect on the serum protein binding of bilirubin, salicylic acid, and sulfisoxazole.

Animals↗