Biomedical subjects

C T Ueda

Publications and source records attributed to C T Ueda.

22 records · Page 2Linked to original sources

PubMedDate not supplied

Amiodarone pharmacokinetics. II. Disposition kinetics following subchronic administration in rats.

A 30 mg kg-1 intravenous bolus of 14C-amiodarone (19 microCi kg-1) was given to male Sprague-Dawley rats pretreated with 0 (vehicle), 25 or 100 mg kg-1 day-1 of amiodarone HCl orally for 37-42 days to determine the effects of dose and duration of administration on the disposition kinetics of amiodarone. Serial blood samples and total urine were collected over 48 hours and assayed for 14C-amiodarone by liquid scintillation counting following separation by HPLC. In all three groups, the blood 14C-amiodarone concentration-time curves declined bioexponentially with terminal half-lives (t1/2 beta) ranging from 14-22 hours. No differences in beta, t1/2 beta, or central compartment volume (Vc) were observed between the three groups of rats. In the rats pretreated with 100 mg kg-1 day-1 of amiodarone HCl for 5-6 weeks, amiodarone clearance (CL) and steady state volume of distribution (Vss) were reduced 52 per cent (12.2 to 5.9 ml min-1 kg-1) and 41 per cent (11.73 to 6.97 l kg-1), respectively. At the lower amiodarone daily dose, no changes in CL or Vss were observed. Negligible levels of radioactivity were detected in the urine. Amiodarone accounted for approximately 30-40 per cent of the total radioactivity in each blood specimen. This study demonstrated that CL and Vss were dose-dependent, and that beta, t1/2 beta and Vc were dose-independent. The results further suggested that the disposition kinetics of amiodarone were independent of the duration of drug administration.

Amiodarone↗

PubMedDate not supplied

Further observations on the disposition characteristics of salicylic acid in analbuminemic rats.

The disposition characteristics of salicylic acid (SA) were investigated in analbuminemic rats after intravenous bolus injection of 10 and 173 mg kg-1 of SA to study the effects of plasma protein binding on drug disposition. Following the administration of 10 mg kg-1 of SA, total body SA clearance (CL) was markedly faster and its apparent volume of distribution (Vd) significantly greater in the analbuminemic rats in comparison to the controls. Further, the apparent elimination rate constant (kj) was two-fold greater and the corresponding elimination half-life (t 1/2) shorter in the rats with low plasma albumin. Whole body autoradiograms obtained following the administration of 14C-salicylic acid demonstrated that the tissue distribution of SA was greater in the analbuminemic rats which was in agreement with the larger Vd observed in this group of rats. After the administration of 173 mg kg-1 of SA, no differences in CL, Vd, kk or t 1/2 were noted between the analbuminemic and control rats. Dose-dependent SA disposition was observed in both the analbuminemic and control rats with the effects being more pronounced in the rats with low plasma albumin. The results suggested that the disposition characteristics of SA were markedly altered in the presence of low plasma albumin concentrations due to reduced plasma SA protein binding.

Animals↗

PubMedDate not supplied

Comparative bioavailability characteristics of commercial quinidine polygalacturonate and sulfate tablets.

This study compared the relative bioavailability characteristics of quinidine polygalacturonate (QP) and quinidine sulfate (QS) after oral administration of commercial tablets and a liquid form prepared from crushed tablets in 13 healthy adult male volunteers. Each subject received the following four single-dose treatments in a randomized, crossover manner with a one-week washout period between treatments: 400 mg QS liquid, two 200-mg QS tablets, 550 mg QP liquid, and two 275-mg QP tablets. All four treatments were equivalent in terms of the dose of quinidine base. Multiple serum samples and two 24-hour urine specimens were collected over 24 and 48 hours, respectively, and assayed for quinidine with a specific HPLC assay method. For the absorption and disposition parameters measured (maximum serum concentration, time to reach maximum concentration, area under the concentration-time curve [0-48 hours], absorption and elimination rate constants, absorption and elimination half-lives, apparent total body clearance, apparent volume of distribution, and dose fraction excreted in the urine) no significant differences were observed for any of the parameters among the four treatments (p greater than 0.05). The results of the present investigation demonstrated that QP and QS produced identical serum quinidine concentration-time curves when given in the form of a tablet or liquid. The clinical implications of these observations with respect to the dosing of QP are discussed.

Adult↗

PubMedDate not supplied

Phenytoin disposition in the pregnant rat. Dose-dependent studies and salicylate effects.

Studies were conducted in 19-day gestation Sprague-Dawley rats to investigate the dose dependency and effects of salicylate coadministration on phenytoin disposition during pregnancy. After iv loading doses of both drugs, concurrent iv infusions of 75.6, 151.2, or 302.4 micrograms/min/kg of 14C-phenytoin and 65, 130, or 195 micrograms/min/kg of salicylate were administered for 180 min. Maternal plasma, fetal plasma, and whole fetus samples were obtained during the infusions, and maternal tissue (heart, skeletal muscle, fat, liver, and brain) and cerebrospinal fluid specimens were collected at the termination of drug administration. All samples were assayed for phenytoin and p-hydroxydiphenylhydantoin by liquid scintillation counting following separation by TLC. Systemic and intrinsic phenytoin clearance, which averaged 12 and 41.5 ml/min/kg, respectively, for the three phenytoin infusions, were both dose independent, and were unaltered by the three salicylate treatments. Similarly, the maternal tissue-to-plasma concentration ratios for phenytoin and p-hydroxydiphenylhydantoin were dose and/or concentration independent following the three phenytoin infusions, and were also not affected by salicylate coadministration. Additionally, the fetal distribution ratios for whole fetus-to-maternal plasma and whole fetus-to-fetal plasma were also invariant for the three phenytoin infusions and salicylate treatments. The results showed that the maternal and fetal disposition of phenytoin was dose and concentration independent and unaltered by salicylate coadministration with the dosages studied.

Animals↗