Pharmacokinetics and renal handling of enprofylline in pregnant rats

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)653-657
Number of pages5
JournalDrug Metabolism and Disposition
Volume20
Issue number5
Publication statusPublished - 01-01-1992
Externally publishedYes

Fingerprint

Pharmacokinetics
Kidney
Pregnancy
Protein Binding
enprofylline
Aptitude
Postpartum Period
Sprague Dawley Rats
Blood Proteins
Albumins

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Muraoka, I. ; Hasegawa, T. ; Nadai, M. ; Kato, K. ; Nabeshima, Toshitaka. / Pharmacokinetics and renal handling of enprofylline in pregnant rats. In: Drug Metabolism and Disposition. 1992 ; Vol. 20, No. 5. pp. 653-657.
@article{23fc554c9d6d4c85bc77ab6fc689bde9,
title = "Pharmacokinetics and renal handling of enprofylline in pregnant rats",
abstract = "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.",
author = "I. Muraoka and T. Hasegawa and M. Nadai and K. Kato and Toshitaka Nabeshima",
year = "1992",
month = "1",
day = "1",
language = "English",
volume = "20",
pages = "653--657",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "5",

}

Muraoka, I, Hasegawa, T, Nadai, M, Kato, K & Nabeshima, T 1992, 'Pharmacokinetics and renal handling of enprofylline in pregnant rats', Drug Metabolism and Disposition, vol. 20, no. 5, pp. 653-657.

Pharmacokinetics and renal handling of enprofylline in pregnant rats. / Muraoka, I.; Hasegawa, T.; Nadai, M.; Kato, K.; Nabeshima, Toshitaka.

In: Drug Metabolism and Disposition, Vol. 20, No. 5, 01.01.1992, p. 653-657.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacokinetics and renal handling of enprofylline in pregnant rats

AU - Muraoka, I.

AU - Hasegawa, T.

AU - Nadai, M.

AU - Kato, K.

AU - Nabeshima, Toshitaka

PY - 1992/1/1

Y1 - 1992/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026673890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026673890&partnerID=8YFLogxK

M3 - Article

C2 - 1358568

AN - SCOPUS:0026673890

VL - 20

SP - 653

EP - 657

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 5

ER -