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Drugs in Lactation

Abstract

One impediment to breastfeeding is the lack of information on the use of many drugs during lactation, especially newer ones. The principles of drug passage into breastmilk are well established, but have often not been optimally applied prospectively. Commonly used preclinical rodent models for determining drug excretion into milk are very unreliable because of marked differences in milk composition and transporters compared to those of humans. Measurement of drug concentrations in humans remains the gold standard, but computer modeling is promising. New FDA labeling requirements present an opportunity to apply modeling to preclinical drug development in place of conventional animal testing for drug excretion into breastmilk, which should improve the use of medications in nursing mothers.

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Abbreviations

AUC:

Area under the concentration-time curve

CL:

Total body drug clearance

Cp:

Drug concentration in plasma

CYP2D6:

Cytochrome P450 2D6

F:

Bioavailability

FDA:

U.S. Food and Drug Administration

HIV:

Human immunodeficiency virus

I/M:

Infant to maternal plasma concentration ratio

M/P:

Milk to plasma concentration ratio

PBPK:

Physiologically based pharmacokinetic

PLLR:

Pregnancy and Lactation Labeling Rule

PopPK:

Population pharmacokinetics

QSAR:

Quantitative structure-activity relationship

RID:

Relative infant dose

WHO:

World Health Organization

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Correspondence to Philip O. Anderson.

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The author thanks Edmund Capparelli, Pharm. D. for his review of the manuscript and helpful suggestions. The author declares no competing financial interests.

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Anderson, P.O. Drugs in Lactation. Pharm Res 35, 45 (2018). https://doi.org/10.1007/s11095-017-2287-z

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KEY WORDS

  • breast feeding
  • drug excretion
  • human milk
  • modeling
  • pharmacokinetics