Alpha 2.0
Login Register
» Articles » PMID: 6491898

A Physiologically Based Pharmacokinetic Model for Theophylline Disposition in the Pregnant and Nonpregnant Rat

Overview
Journal J Pharmacokinet Biopharm
Specialty Pharmacology
Date 1984 Apr 1
PMID 6491898
Citations 6
Authors
J L Gabrielsson
L K Paalzow
L Nordstrom
Affiliations
Soon will be listed here.
Abstract

There are numerous studies which examine the disposition of theophylline from a traditional point of view. Information about the behaviour of drugs, including theophylline, is, however, very scarce when investigating the kinetics by means of a physiological flow model. This study is concerned with the development of a predictive analytical model for the pharmacokinetics of theophylline in nonpregnant and pregnant rats. This model postulates that specific organ or tissue masses may be simulated by compartments whose elements have physiological properties, e.g., tissue volumes, blood flow, and metabolic activity. A model has been developed that has blood, brain, hepatic, muscular, pulmonary, renal, and fetal tissues. With few exceptions, the agreement was good between predicted and calculated tissue data in the pregnant and nonpregnant rats. Finally, model simulations were performed to investigate the impact of different pulmonary extraction ratios on the concentration-time profile of theophylline in a "hypothetical" human patient.

Citing Articles

The Application of a Physiologically Based Toxicokinetic Model in Health Risk Assessment.

Chen M, Du R, Zhang T, Li C, Bao W, Xin F Toxics. 2023; 11(10).

PMID: 37888724 PMC: 10611306. DOI: 10.3390/toxics11100874.

Prediction of in vivo tissue distribution from in vitro data. 3. Correlation between in vitro and in vivo tissue distribution of a homologous series of nine 5-n-alkyl-5-ethyl barbituric acids.

Ballard P, Leahy D, Rowland M Pharm Res. 2003; 20(6):864-72.

PMID: 12817889 DOI: 10.1023/a:1023912318133.

Prediction of in vivo tissue distribution from in vitro data. 2. Influence of albumin diffusion from tissue pieces during an in vitro incubation on estimated tissue-to-unbound plasma partition coefficients (Kpu).

Ballard P, Arundel P, Leahy D, Rowland M Pharm Res. 2003; 20(6):857-63.

PMID: 12817888 DOI: 10.1023/a:1023879001294.

Area method for the estimation of partition coefficients for physiological pharmacokinetic models.

Gallo J, Lam F, Perrier D J Pharmacokinet Biopharm. 1987; 15(3):271-80.

PMID: 3668804 DOI: 10.1007/BF01066322.

A semiparametric approach to physiological flow models.

Verotta D, Sheiner L, Ebling W, Stanski D J Pharmacokinet Biopharm. 1989; 17(4):463-91.

PMID: 2614682 DOI: 10.1007/BF01061458.

References
1.
Arnaud M, Bracco I, Welsch C . Metabolism and distribution of labeled theophylline in the pregnant rat. Impairment of theophylline metabolism by pregnancy and absence of a blood-brain barrier in the fetus. Pediatr Res. 1982; 16(3):167-71. DOI: 10.1203/00006450-198203000-00001. View
2.
Gabrielsson J, Paalzow L . A physiological pharmacokinetic model for morphine disposition in the pregnant rat. J Pharmacokinet Biopharm. 1983; 11(2):147-63. DOI: 10.1007/BF01061846. View
3.
Heymann M . Interrelations of fetal circulation and the placental transfer of drugs. Fed Proc. 1972; 31(1):44-7. View
4.
Neese A, SOYKA L . Toxicity and tissue distribution of aminophyline in neonatal and adult mice and rats. Pediatr Res. 1977; 11(6):783-6. DOI: 10.1203/00006450-197706000-00018. View
5.
Bonati M, Latini R, Marra G, Assael B, Parini R . Theophylline distribution in the premature neonate. Dev Pharmacol Ther. 1981; 3(2):65-73. DOI: 10.1159/000457424. View