Correlation of Unbound Plasma Clearances of Fifteen Extensively Metabolized Drugs Between Humans and Rats
Abstract
Unbound plasma clearances (CLu) in humans and rats of 15 extensively metabolized drugs (phenytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, amobarbital, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam), studied earlier by Sawada et al. (J. Pharmacokin, Biopharm. 13:477-491, 1985), were calculated. It was found that the ratio of CLu per square meter of body surface area between human and rat ranged from 0.38 for pentobarbital to 2.34 for tolbutamide, with a mean ratio of 1.07. When body weight (BW) was used for correlation, the mean CLu was proportional to BW 0.657 +/- 0.0935. A rationale for the above empirical findings is postulated. The present study seems to indicate the existence of a general similarity or predictability in the CLu of drugs between rats and humans. Low correlations were generally obtained when total (bound and unbound) plasma clearances were used for comparison.
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Consideration of protein binding to correct inter-species differences in AS tended to improve the prediction of human clearance.
“In their work, consideration of protein binding to correct inter-species differences in AS tended to improve the prediction of human clearance.”
From Interpretation of Non-Clinical Data for Prediction of Human Pharmacokinetic Parameters: In Vitro-In Vivo Extrapolation and Allometric Scaling (2019) · cites this paper as [112]
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ALLOMETRIC SCALING FOR PREDICTING HUMAN DRUG CLEARANCE
Tang, H. (2005) · UA Campus Repository (The University of Arizona)
- Authors
- Chiou, W. L., & Hsu, F.-H.
- Affiliations
- University of Illinois Chicago (US)
- ORCID
- Chiou, Win L.
- Venue
- Pharmaceutical Research
- Published
- 1988-10
- Volume
- 5
- Issue
- 10
- Pages
- 668-672
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W39205234
- Cited by
- 28
- References
- 35
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2019: 1 · 2018: 1 · 2017: 1
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Keywords
- human-rat comparison, body surface area, body weight, drug metabolism, phenytoin, barbiturates, antiepileptic drugs, antipsychotic drugs, antihypertensive drugs, antipyrine, diazepam, warfarin, quinidine, chlorpromazine, propranolol, tolbutamide, valproic acid
- MeSH terms
- Animals, Body Surface Area, Pharmaceutical Preparations, Humans, Liver, Male, Species Specificity, Rats
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