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H Y Yu

Publications and source records attributed to H Y Yu.

82 records · Page 5Linked to original sources
PubMed1981

Effect of sulfadimethoxine on thiopental distribution and elimination in rats.

The effect of sulfadimethoxine on the distribution and elimination of thiopental was examined by comparing the change in the steady-state volume of distribution (Vss) determined from both in vivo plasma elimination and in vitro serum and tissue binding studies in rats. The plasma disappearance of thiopental after a 12-mg/kg iv dose followed a biexponential decline in both the control and sulfadimethoxine-treated rats. The plasma thiopental concentrations under the steady-state plasma sulfadimethoxine concentration (500 micrograms/ml) were significantly lower than those of the control rats. In the sulfadimethoxine-treated rats, the pharmacokinetic parameter beta significantly decreased while Vss significantly increased to 3.6-fold that of the control rats. With sulfadimethoxine, a significant increase was observed in the apparent dissociation constant (Kd) of thiopental to serum protein by equilibrium dialysis, but the total number of binding sites was not altered. The in vitro serum free fraction of thiopental was increased to about 2.6-fold in the presence of sulfadimethoxine. The free fraction of thiopental in the main distribution tissues (liver, muscle, and adipose) was determined by equilibrium dialysis with and without sulfadimethoxine. No significant changes were observed in the presence of sulfadimethoxine. The calculated Vss, determined by the free fractions from in vitro binding experiments, also showed a significant increase. The ratio of Vss with sulfadimethoxine to that of the control rats was 2.8. The total clearance did not change, but the intrinsic clearance decreased to one-half of that of the control rats due to the increase of the serum free fraction by sulfadimethoxine. It was concluded that sulfadimethoxine caused a displacement of thiopental in plasma protein binding, which significantly increased the free fraction of thiopental, and this result may explain the significant increase of Vss and the decrease of both beta and intrinsic clearance. Tissue binding of thiopental, however, was unaffected by sulfadimethoxine.

Animals↗
PubMedDate not supplied

Changes in pharmacokinetics of valproic acid in guinea pigs from birth to maturity.

Pharmacokinetic variations of valproic acid in guinea pigs from birth to maturity were investigated. Male guinea pigs were classified into three groups according to age, and each group was further divided into two to three subgroups. The suckling group included three subgroups of 3, 6, and 10 days of age; the juvenile group, three subgroups of 14, 21, and 28 days of age; and the adult group, two subgroups of 42 and 56 days of age. The bile was exteriorized to exclude the factor of enterohepatic circulation during the experiment. Pharmacokinetic parameters were studied and statistically analyzed after an intravenous single dose of 20 mg/kg of sodium valproate. A significantly (p less than 0.01) longer elimination half-life (t1/2) in guinea pigs less than 10 days of age compared with other groups was observed. Total clearance (Cltot) was significantly smaller (p less than 0.01) in the suckling group than in the juvenile group. Volume of distribution at steady state (Vss) was not significantly different between the suckling and juvenile groups, but was significantly smallest (p less than 0.01) in the adult group. In vitro study showed that the blood-to-plasma concentration ratio, ranging from 0.81 to 0.84, and the plasma unbound fraction (fu), ranging from 0.24 to 0.38, of valproic acid around therapeutic levels (50-100 micrograms/ml) were not significantly different among different age groups. It is obvious that the longer t1/2 in the suckling group is not related to either fu or Vss.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMedDate not supplied

Dose-dependent pharmacokinetics of valproate in guinea pigs of different ages.

The dose-dependence of sodium valproate (VPA) pharmacokinetics in relation to age was studied using guinea pigs. Sodium valproate in doses of 20, 200, and 600 mg/kg was administered by rapid intravenous infusion to male guinea pigs 3, 21, and 42 days old. Serum levels of VPA were determined by gas chromatography. Pharmacokinetic parameters were calculated based upon a two-compartment model. The area under the plasma concentration-time curve (AUC) increased out of proportion at the 600 mg/kg dose level in all groups. Other pharmacokinetic changes were as follows: in 3-day-old guinea pigs, the slow disposition rate constant (beta), the elimination rate constant from central compartment (K10), and the total clearance (Clt) were significantly decreased and the beta phase half-life (t 1/2) and the volume of central compartment (V1) were significantly increased at the 600 mg/kg dose level. In 21-day-old guinea pigs, beta and K10 were significantly decreased and t1/2 and V1 were significantly increased at doses of both 200 mg/kg and 600 mg/kg. In 42-day-old guinea pigs, however, only V1 and the volume of distribution at steady-state (Vss) showed significant increase after increasing doses. The extraction ratio (E) and the clearance of unbound drug (Clu), which were calculated based on unbound plasma levels, indicate that the dose-dependent kinetics of VPA are probably due to saturation of metabolism and that the metabolic capacity for VPA in the newborn group is the smallest among all groups.

Aging↗
PubMedDate not supplied

Drug interaction. Effects of salicylate on pharmacokinetics of valproic acid in rats.

The effects of salicylic acid on the pharmacokinetics of valproic acid were investigated in bile-exteriorized rats. A 50 mg/kg bolus dose of sodium valproate was injected iv to Long Evans rats with and without (control) prior treatment by constant infusion of salicylate to keep it at steady state plasma level (about 250 micrograms/ml). The plasma elimination of valproic acid followed a monoexponential decline in both salicylate-treated and control rats. A significant increase (p less than 0.01) in the disposition rate constant (kel), the volume of distribution (Vd), and the total clearance (Cltot) as well as a significant decrease (p less than 0.01) in the AUC and the elimination half-life (t1/2) were observed in the salicylate-treated rats. In spite of the significantly lowered total plasma level and increased unbound fraction of valproic acid in the salicylate-treated rats, there were no significant differences in unbound valproic plasma levels and unbound valproate pharmacokinetic parameters. The biliary excretion of unchanged and conjugated valproate was not significantly different between the two groups. The in vitro plasma-unbound fractions (fu) of valproic acid were significantly increased (p less than 0.01) in the presence of salicylic acid. The apparent dissociation constant of plasma protein binding for valproic acid was increased from 0.287 to 1.204 mM in the presence of salicylic acid. These findings indicate that the pharmacokinetic changes of valproic acid in the presence of salicylic acid were consistent with the elevation in the plasma-unbound fraction of valproic acid due to displacement from plasma protein-binding sites by salicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗