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Pharmacologic Factors Contributing to Variance in the Milk to Plasma Ratio for Acetaminophen in the Goat

Pharmacologic Factors Contributing to Variance in the Milk to Plasma Ratio for Acetaminophen in... A single-point estimate of the milk to plasma (M/P) drug ratio presupposesan invariant ratio. This may lead to erroneous conclusions about the amount of drugexcreted in breast milk. A variance of the M/P ratio with regard to time has been shownfor acetaminophen under standardized biologic conditions in the lactating goat. This ratiois potentially confounded by such factors as route of administration, dose amount andduration of exposure to the drug. Each factor was evaluated by computer simulations ofthe M/P ratio and by derivation of a ratio from empirical data in the goat. Route ofadministration was found to influence both the pattern and magnitude of the M/P ratioafter acetaminophen dosing in the goat. Similar, but less, effects were found for durationof dosing. Dose itself did not influence the ratio. A temporal basis exists for each confoundingfactor. We thus propose that the M/P ratio is fundamentally variant with timeunder a standard set of biologic conditions. The contributing variance of confoundingfactors must be assessed if drug in milk dosing of the infant is to be accurately evaluatedby use of the M/P ratio. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Developmental Pharmacology and Therapeutics Karger

Pharmacologic Factors Contributing to Variance in the Milk to Plasma Ratio for Acetaminophen in the Goat

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Publisher
Karger
Copyright
© 1987 S. Karger AG, Basel
ISSN
0379-8305
eISSN
2504-2505
DOI
10.1159/000457728
Publisher site
See Article on Publisher Site

Abstract

A single-point estimate of the milk to plasma (M/P) drug ratio presupposesan invariant ratio. This may lead to erroneous conclusions about the amount of drugexcreted in breast milk. A variance of the M/P ratio with regard to time has been shownfor acetaminophen under standardized biologic conditions in the lactating goat. This ratiois potentially confounded by such factors as route of administration, dose amount andduration of exposure to the drug. Each factor was evaluated by computer simulations ofthe M/P ratio and by derivation of a ratio from empirical data in the goat. Route ofadministration was found to influence both the pattern and magnitude of the M/P ratioafter acetaminophen dosing in the goat. Similar, but less, effects were found for durationof dosing. Dose itself did not influence the ratio. A temporal basis exists for each confoundingfactor. We thus propose that the M/P ratio is fundamentally variant with timeunder a standard set of biologic conditions. The contributing variance of confoundingfactors must be assessed if drug in milk dosing of the infant is to be accurately evaluatedby use of the M/P ratio.

Journal

Developmental Pharmacology and Therapeutics – Karger

Published: Jan 1, 2017

Keywords: Breast milk; Milk/plasma ratio; Pharmacokinetics; Acetaminophen; Goat

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