Title

Examination of Urinary Excretion of Unchanged Drug in Humans and Preclinical Animal Models: Increasing the Predictability of Poor Metabolism in Humans.

Document Type

Article

Publication Date

7-2021

Identifier

DOI: 10.1007/s11095-021-03076-y

Abstract

Purpose: A dataset of fraction excreted unchanged in the urine (fe) values was developed and used to evaluate the ability of preclinical animal species to predict high urinary excretion, and corresponding poor metabolism, in humans.

Methods: A literature review of fe values in rats, dogs, and monkeys was conducted for all Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3 and 4 drugs (n=352) and a set of Class 1 and 2 drugs (n=80). The final dataset consisted of 202 total fe values for 135 unique drugs. Human and animal data were compared through correlations, two-fold analysis, and binary classifications of high (fe ≥30%) versus low (

Results: Significant correlations were found between fe values for each animal species and human fe (p

Conclusions: Drugs with high urinary excretion in animals are likely to have high urinary excretion in humans. Animal models tend to underpredict the urinary excretion of unchanged drug in humans.

Journal Title

Pharmaceutical research

Volume

38

Issue

7

First Page

1139

Last Page

1156

Keywords

BDDCS; Fraction excreted unchanged; animal models; poorly-metabolized drugs; renal clearance

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