Authors
Leslie Z Benet, Jasleen K Sodhi
Published in
Annual review of pharmacology and toxicology. Aug 14, 2026. Epub Aug 14, 2026.
Abstract
We review a new methodology for deriving pharmacokinetic clearance equations independent of differential equations or mechanistic models of drug disposition. Nine examples are presented that illustrate the application of this framework to drug dosing decisions based on therapeutic monitoring. Although mass balance is necessary and sufficient in deriving in vitro measures and rate constants relevant to in vivo pharmacokinetics, clinical drug dosing decisions are based on clearance, not rate constants. Mass balance is necessary in deriving pharmacokinetic clearance equations, but in vivo it is not always sufficient in determining which processes drive overall clearance. A key implication of this framework is that pharmaceutical sponsors may possibly formulate a dosage form for high-clearance drugs, where the manufactured delivery clearance from the dosage form becomes the in vivo clearance of drug in the patient, independent of the elimination clearance observed following an intravenous bolus dose and independent of the patient-specific characteristics.
PMID:
42599950
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.
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