Longitudinal Effects of Pregnancy on the Pharmacokinetics of Theophylline

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 1987 Jan 1

PMID 3595701

Citations 9

Authors

M J Gardner

M Schatz

L Cousins

R Zeiger

E Middleton

W J Jusko

Affiliations

Soon will be listed here.

Abstract

The effects of pregnancy on the disposition of theophylline were assessed in 10 patients throughout pregnancy and post-partum. The clearance relative to total theophylline concentrations was only slightly affected during the first two trimesters (2.61 +/- 0.63 l/h and 2.85 +/- 1.05 l/h), while a statistically significant reduction was evident late in pregnancy (2.05 +/- 0.49 l/h). Post-partum clearance values (2.16 +/- 2.81 l/h) suggest an ongoing suppression relative to pre-pregnancy levels. A similar pattern was evident with clearance values based on free theophylline plasma concentrations (p = 0.12). Absolute volume of distribution increased in concert with gestation, suggesting that theophylline partitions into the enlarged tissue spaces. In addition, theophylline binding to plasma proteins decreased, albeit insignificantly, during the second (fraction bound = 29%) and third (32%) trimesters compared to post-partum values (41%). Increases in half-life during the third trimester (13.00 +/- 2.31 h vs 9.53 +/- 3.53 h post-partum) were highly significant. This change reflects the net effect of reduced clearance and increased distribution. Breast feeding had no effect on the disposition of theophylline, although the transfer of this compound into breast milk was confirmed.

Citing Articles

Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations.

Abduljalil K, Gardner I, Jamei M Front Pediatr. 2022; 10:840710.

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Piperaquine Exposure Is Altered by Pregnancy, HIV, and Nutritional Status in Ugandan Women.

Hughes E, Imperial M, Wallender E, Kajubi R, Huang L, Jagannathan P Antimicrob Agents Chemother. 2020; 64(12).

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Physiologically Based Pharmacokinetic Modeling of Renally Cleared Drugs in Pregnant Women.

Dallmann A, Ince I, Solodenko J, Meyer M, Willmann S, Eissing T Clin Pharmacokinet. 2017; 56(12):1525-1541.

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A physiologically based pharmacokinetic model to predict disposition of CYP2D6 and CYP1A2 metabolized drugs in pregnant women.

Ke A, Nallani S, Zhao P, Rostami-Hodjegan A, Isoherranen N, Unadkat J Drug Metab Dispos. 2013; 41(4):801-13.

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Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling.

Abduljalil K, Furness P, Johnson T, Rostami-Hodjegan A, Soltani H Clin Pharmacokinet. 2012; 51(6):365-96.

PMID: 22515555 DOI: 10.2165/11597440-000000000-00000.

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