PMID: 3772739Aug 1, 1986Paper

Analysis of pethidine disposition in the pregnant rat by means of a physiological flow model

Journal of Pharmacokinetics and Biopharmaceutics
J GabrielssonL Paalzow

Abstract

The disposition of pethidine (meperidine) in the pregnant rat is described by means of a physiological flow model. The model includes arterial and venous blood, brain, fat, fetal, hepatic, intestinal, muscular, pulmonar, and renal tissues. The concentration-time profiles of pethidine calculated by the model are consistent with experimental data, except for the brain and renal tissues, where the model predicts initially higher concentrations. Simulations are carried out to further explore the contribution from different organs on the kinetics in blood and tissues. The tissue-to-blood partition coefficients vary over a range from 5 to 316, where fat has the lowest and liver the highest after a correction is made due to hepatic extraction. Rapid uptake occurs into highly perfused organs such as brain, kidneys, liver, and lungs, followed by fetus, intestines, muscle, and fat. Data indicate no marked membrane resistance to pethidine of the investigated organs, except for fetal tissues, but rather a perfusion-limited uptake. Simulations suggest that muscles and adipose tissue play an important role in the rat, becoming the major reservoir of drug during the intermediate and terminal elimination phase, respectively. Volume of distribu...Continue Reading

References

Sep 1, 1978·Clinical Pharmacokinetics·L E Mather, P J Meffin
Mar 1, 1978·Clinical Pharmacology and Therapeutics·D MorganE Triggs
May 1, 1985·Journal of Pharmaceutical Sciences·W G KramerC Medlock
Aug 1, 1985·Journal of Pharmacokinetics and Biopharmaceutics·J L GabrielssonL K Paalzow
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Citations

Dec 1, 1993·Journal of Veterinary Pharmacology and Therapeutics·G L Qiao, K F Fung
Jan 1, 1990·Pharmacology & Toxicology·J L Gabrielsson, K S Larsson
Feb 1, 1988·British Journal of Clinical Pharmacology·M P PerssonL Paalzow
Jun 1, 1993·Journal of Pharmacokinetics and Biopharmaceutics·S BjörkmanW F Ebling
Feb 23, 2019·The Journal of Pharmacy and Pharmacology·Ioannis Loisios-KonstantinidisJennifer Dressman

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