ArticleEuropean journal of drug metabolism and pharmacokinetics
Allometric scaling of pharmacokinetic parameters in drug discovery: can human CL, Vss and t1/2 be predicted from in-vivo rat data?
Article in European journal of drug metabolism and pharmacokinetics. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
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- Fraction-based Linear Extrapolation (FLEX) Method for Predicting Human Pharmacokinetic Clearance: Advanced Allometric Scaling Method and Machine Learning Approach.Pharmaceutical research · 2025Article
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- Assessing Boron-Pleuromutilin AN11251 for the Development of Antibacterial Agents.Molecules (Basel, Switzerland) · 2023Article
- Application of the Population Pharmacokinetics Model-Based Approach to the Prediction of Drug-Drug Interaction between Rivaroxaban and Carbamazepine in Humans.Pharmaceuticals (Basel, Switzerland) · 2023Article
- In Vitro-In Vivo Extrapolation and Scaling Factors for Clearance of Human and Preclinical Species with Liver Microsomes and Hepatocytes.The AAPS journal · 2023Article
- Preclinical Pharmacokinetics and Safety of Intravenous RTD-1.Antimicrobial agents and chemotherapy · 2022Article
- RTICBM-74 Is a Brain-Penetrant Cannabinoid Receptor Subtype 1 Allosteric Modulator that Reduces Alcohol Intake in Rats.The Journal of pharmacology and experimental therapeutics · 2022Article
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4 authors.
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Abstract
In a drug discovery environment, reasonable go/no-go human in-vivo pharmacokinetic (PK) decisions must be made in a timely manner with a minimum amount of animal in-vivo or in-vitro data. We have investigated the accuracy of the in-vivo correlation between rat and human for the prediction of the total systemic clearance (CL), the volume of distribution at steady state (Vss), and the half-life (t1/2) using simple allometric scaling techniques. We have shown, using a large diverse set of drugs, that a fixed exponent allometric scaling approach can be used to predict human in-vivo PK parameters CL, Vss and t(1/2) solely from rat in-vivo PK data with acceptable accuracy for making go/no-go decisions in drug discovery. Human in-vivo PK predictions can be obtained using the simple allometric scaling relationships CL(Human) approximately = 40 CL(Rat) (L/hr), Vss(Human) approximately = 200 Vss(Rat) (L), and t1/2(Human) approximately = 4 t1/2(Rat) (hr). The average fold error for human CL predictions for N = 176 drugs was 2.25 with 79% of the drugs having a fold error less than 3. The average fold error for human Vss predictions for N = 144 drugs was 1.85 with 84% of the drugs having a fold error less than 3. The average fold error for human t1/2 predictions for N = 145 drugs was 2.05 with 76% of the drugs having a fold error less than 3. Using these simple allometric relationships, the sorting of drug candidates into a low/medium/high/very high human classification scheme was also possible from rat data. Since these simple allometric relationships between rat and human CL, Vss, and t1/2 are reasonably accurate, easy to remember and simple to calculate, these equations should be useful for making early go/no-go in-vivo human PK decisions for drug discovery candidates.
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