Transdermal absorption and skin metabolism of viprostol, a synthetic prostaglandin E2 analogue.
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Animals↗
Biomedical subjects
A Yacobi
Publications and source records attributed to A Yacobi.
Serum protein binding of a new oral cephalosporin, CL 284,635, in various species.
CL 284,635 is a new third generation oral cephalosporin. Its serum protein binding was investigated in the human, monkey, dog, rat, and rabbit. This study was performed by using an equilibrium dialysis and ultrafiltration method, using radiolabeled and cold CL 284,635. In humans, CL 284,635 was found to have a mean free fraction [fu = concentration of unbound (free) drug divided by total concentration of unbound plus bound to serum proteins] of 31.3 +/- 3.3% with no serum concentration dependency in a range of 0.5 to 26 micrograms/ml. The drug was mainly bound to albumin. In rabbits and monkeys the protein binding profile of CL 284,635 was found to be 36.1 +/- 2.3% and 33.9 +/- 1.5% with no serum concentration dependency. In rats and dogs a non-concentration-dependent fu was observed at serum concentrations ranging from 0.5 to 30 micrograms/ml. A gradual increase in fu values was observed at higher serum concentrations of CL 284,635. Overall, the protein binding profile of CL 284,635 was found to be different in the five investigated species. The protein binding of CL 284,635 in monkeys and rabbits was most similar to that in humans. These species differences in protein binding may have an impact on the disposition of the drug in different species.
Animals↗
Disposition of cefixime in the pregnant and lactating rat. Transfer to the fetus and nursing pup.
The disposition of cefixime, a potent, third generation, orally active cephalosporin, was characterized in the pregnant and lactating rat. After a single iv dose of 17.8 mg/kg 14C-cefixime to day 18 pregnant rats, the half-life for elimination of radioactivity from both maternal serum and placentas was 6.9 hr. Elimination from fetal plasma and tissues was somewhat longer, 12.5 and 13.7 hr, respectively. However, comparison of areas under the curve indicated that exposure of the fetuses to cefixime was far less than that of placentas. Whole body autoradiography showed the greatest radioactivity in maternal liver, kidney, and intestines. In the lactating rat, steady state plasma concentrations of 14C-cefixime were achieved by continuous ip infusion of 2.54 mg/kg/day via Alza osmotic Mini-pumps from days 10 to 14 postpartum. Plasma concentrations of radioactivity in the dams were, on the average, 70 times greater than in their nursing pups throughout the study. After 102 hr of drug infusion, total radioactivity in the body of the pups, including the stomach and intestinal contents, was 1% of the 14C-cefixime estimated to be in the mother's body at steady state. Overall, these data indicate that exposure of the developing rat fetus and nursing pup to cefixime after maternal drug administration is quantitatively small.
Animals↗
Relationship between the pharmacokinetic and pharmacodynamic profile of nilvadipine in the dog.
The purpose of this study was to determine the pharmacokinetic profile of nilvadipine and, using a chronic dog model, determine whether there was a correlation between plasma concentrations of the drug and hemodynamic effects. Nilvadipine was given to four dogs as single intravenous (iv) and oral doses. Pharmacokinetic parameters were estimated after each dose using model-independent methods. The mean elimination half-life was approximately 6 hr after both iv and oral doses. The absolute bioavailability of nilvadipine decreased from 67 to 27% after increasing oral doses (6 and 24 mg), probably because of reduced drug absorption from the gastrointestinal tract. Nilvadipine produced plasma concentration-related decreases in diastolic (DBP) and systolic (SBP) blood pressure and reflex increases in heart rate. The maximum reduction in DBP and SBP ranged from 34 to 53% and 17 to 47%, respectively, from control and was attained at about 0.1 and 0.7 hr after iv and oral doses, respectively. A strong linear correlation between the per cent reduction in both DBP (r = 0.9; p less than 0.001) and SBP (r = 0.66; p less than 0.001) and log plasma concentration of nilvadipine was established. The slopes of the concentration-response relationships were virtually superimposable after both iv and oral routes of administration. A plasma concentration of about 10 and 16 ng/ml was associated with a 14% reduction in DBP or SBP, respectively. There was no clear relationship between plasma concentrations of nilvadipine and changes in heart rate.
Administration, Oral↗
Tissue distribution of N-acetylprocainamide in rats.
The purpose of this study was to determine the distribution of N-acetylprocainamide (NAPA) in heart, kidney, and liver tissues of rats and their relationship to the plasma concentration after intravenous administration of the drug (100 mg/kg) to 24 Charles River rats. A specific HPLC procedure was used. The plasma and tissue concentrations of NAPA declined biexponentially in parallel, with an elimination half-life of about 1.8 hr. The equilibrium between plasma and the organs tested in this study was attained within 5 min. The tissue/plasma concentration ratio remained constant throughout the study. The tissue/plasma ratios for heart, kidney, and liver were 2.1, 7.9, and 2.4, respectively. The data indicate that: a) these organs have greater affinity to NAPA than do plasma proteins, and b) plasma concentrations may be reliable measures of the therapeutically effective concentrations at the site of action, i.e., the heart tissues.
Acecainide↗