Pharmacokinetics and renal handling of enprofylline in pregnant rats

I. Muraoka, T. Hasegawa, M. Nadai, K. Kato, T. Nabeshima

研究成果: Article査読

3 被引用数 (Scopus)

抄録

The pharmacokinetics and renal handling of enprofylline during pregnancy were investigated in Sprague-Dawley rats. Significant differences in the pharmacokinetic parameters of enprofylline were observed between nonpregnant rats and pregnant rats on the 20th day of gestation: volume of distribution was higher, and systemic clearance was lower in pregnant rats. Parameters obtained from rats at 7 days postpartum were the same as those obtained from non-pregnant rats. There were no significant differences in the fraction of urinary excretion of enprofylline between nonpregnant and pregnant rats. The protein binding of enprofylline in the plasma of pregnant rats was significantly lower than in nonpregnant rats, as a decrease in the albumin concentration consequentially reduced the binding capacity of enprofylline. The volume of distribution for unbound enprofylline in pregnant rats was not significantly different from nonpregnant rats, although a significant decrease was observed in pregnant rats in the systemic clearance for unbound enprofylline. In addition, the clearance ratio was lower in pregnant rats (2.8) when compared with nonpregnant rats (6.4). Pregnancy caused a decrease in the apparent maximum capacity of transport (V(max)) from 29.9 to 20.8 μg/min and in the Michaelis-Menten constant (K(M)) from 2.59 to 2.26 μg/ml, indicating that the tubular secretion ability of enprofylline becomes reduced during pregnancy. These results suggest that changes that occur in the plasma protein binding behavior and in renal handling as a result of pregnancy are primary factors influencing the disposition of enprofylline during pregnancy.

本文言語English
ページ(範囲)653-657
ページ数5
ジャーナルDrug Metabolism and Disposition
20
5
出版ステータスPublished - 01-01-1992
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学

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