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Biomedical subjects

A Yacobi

Publications and source records attributed to A Yacobi.

At least 91 records · Page 5Linked to original sources
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 Thirty minutes later heart rates were measured and simultaneously a blood sample was withdrawn from each rat.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 Serial blood samples were withdrawn following administration of each tablet, and plasma methaqualone concentrations were determined by an established spectrophotofluormetric assay.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↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXIX: Elimination kinetics and anticoagulant activity of (S)-(-)-warfarin in rats before and after chronic administration.

The kinetics of elimination and the anticoagulant effect of (S)-(-)-warfarin were determined in adult male rats before and after daily drug administration for 13 days. There was a small but statistically significant (p less than 0.05) decrease in the body clearance of (S)-(-)-warfarin (from 4.84 to 4.37 ml/hr/kg) and an increase in the serum free fraction of racemic warfarin (added to serum in vitro) from 0.00850 to 0.0107 (p less than 0.05). The concentration of (S)-(-)-warfarin in serum at which the synthesis rate of prothrombin complex activity is one-half of the pre-warfarin rate increased from 0.532 to 0.655 microgram/ml on the average (p less than 0.05).

Animals↗
PubMed1977

Intraindividual relationships between serum protein binding of drugs in normal human subjects, patients with impaired renal function, and rats.

The serum protein binding of phenytoin, salicylic acid, sulfisoxazole, and warfarin was determined in normal human adults, in patients with impaired renal function (kidney donor and recipient), and in adult male Sprague--Dawley rats. The free fraction values for salicylate and sulfisoxazole were significantly correlated in all three groups. The other correlations were statistically significant in only one or two of these groups. There was a statistically significant negative correlation between albumin concentration and the free fraction values of salicylic acid and sulfisoxazole (but not of phenytoin and only under special circumstances with warfarin) in normal subjects and of phenytoin, salicylic acid, and sulfisoxazole (but not warfarin) in rats. No such correlation was observed for any of the drugs in patients with impaired renal function. These observations show that no single weakly acidic drug can serve as an index for quantitatively determining the effect of disease or species differences on the serum protein binding of other weakly acidic drugs.

Adolescent↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXXI: Effect of plasma protein binding on distribution kinetics of dicumarol in rats.

The purpose of this investigation was to determine, with respect to dicumarol, the effect of plasma protein binding on the pharmacokinetic parameters used conventionally to describe the distribution kinetics of a drug on the basis of the time course of its plasma concentration. After rapid intravenous injection, plasma dicumarol concentrations in adult male Sprague-Dawley rats declined triexponentially, with the terminal exponential phase starting at about 4 hr. The free fraction f, of dicumarol in the serum of individual animals ranged from 0.000150 to 0.000790. The parameters of the equation Ct = Pe-pit + Ae-alphat + Be-betat for plasma concentration Ct at time t were obtained by nonlinear least-squares computer fitting of the experimental data and varied appreciably between animals. Of these parameters, only beta showed a significant correlation with f. These observations indicate that the distribution kinetics of this very extensively plasma protein-bound drug, as reflected by the time course of its plasma concentration after intravenous injection, are apparently not affected by intersubject differences in plasma protein binding. There is a remarkable similarity in the valves of P, A, B, pi, and alpha for dicumarol and warfarin, even though the serum free fraction of these drugs differs considerably.

Animals↗
PubMed1977

Comparative subcutaneous absorption of local anesthetics: lidocaine, procaine and tetracaine.

The pH partition hypothesis was applied to the absorption of ionizable local anesthetic amines through the subcutaneous (s.c.) route. Solutions of lidocaine hydrochloride (LHCl), procaine hydrochloride (PHCl) and tetracaine hydrochloride (THCl) at various pH were implanted on s.c. animal tissue through a glass absorption cell. The s.c. absorption of these drugs was evaluated from the clearances' slopes evolved by determination of the drugs' concentrations in the cell at definite intervals. The higher the pH level, these conjugated bases become more unionized and lipid partitioned resulting in increased rates of s.c. absorption. The extent of unionization is governed by the pka of each of these drugs; at the high feasible pH--procaine which is least unionized--its s.c. absorption rate is nearly a third of that of lidocaine or tetracaine. The pH effect on s.c. absorption of local anesthetics was substantiated by estimation of lethal time50 (LT50) in mice.

Animals↗