Why Half-Life Depends on Clearance and Volume | Clearance, Volume and Half-Life (Excretion 5.4)

Why do some drugs last hours and others days? Lesson 5.4 of our excretion module shows how half-life follows from clearance and the volume of distribution. Midazolam and diazepam show the effect of clearance, and diazepam in obesity shows the effect of volume and the time to steady state. Transcript, equations and practice questions: https://freefraction.com/lessons/5-4-... 0:00 Half-life 1:14 Clearance and volume set k 2:18 The half-life equation 2:45 Effect of clearance 3:25 Effect of volume 4:04 Midazolam and diazepam 4:44 Diazepam in obesity 5:38 Steady state 6:51 Summary Sources Toutain PL, Bousquet-Mélou A. Plasma terminal half-life. J Vet Pharmacol Ther. 2004. PMID 15601438 Holford N. Pharmacodynamic principles and the time course of immediate drug effects. Transl Clin Pharmacol. 2017. PMID 32095468 Yim DS. Tutorial for beginners: the concept of clearance explained using the example of a vacuum cleaner. Transl Clin Pharmacol. 2017. PMID 32095451 Yim DS, Choi S. Predicting human pharmacokinetics from preclinical data: volume of distribution. Transl Clin Pharmacol. 2020. PMID 33425799 Toutain PL, Bousquet-Mélou A. Volumes of distribution. J Vet Pharmacol Ther. 2004. PMID 15601439 Benet LZ, Sodhi JK. Simplifying pharmacokinetics, applying it to drug and dosage form development, and making drug dosage decisions in clinical medicine: the adaptation of Kirchhoff's laws from physics. AAPS J. 2025. PMID 40603610 Abernethy DR, Greenblatt DJ. Phenytoin disposition in obesity: determination of loading dose. Arch Neurol. 1985. PMID 3994563 Smith DA, Beaumont K, Maurer TS, et al. Volume of distribution in drug design. J Med Chem. 2015. PMID 25799158 Smith DA, Beaumont K, Maurer TS, et al. Relevance of half-life in drug design. J Med Chem. 2018. PMID 29112446 Greenblatt DJ, Abernethy DR, Locniskar A, et al. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology. 1984. PMID 6742481 Greenblatt DJ, Allen MD, Harmatz JS, et al. Diazepam disposition determinants. Clin Pharmacol Ther. 1980. PMID 7357789 Abernethy DR, Greenblatt DJ, Divoll M, et al. Prolonged accumulation of diazepam in obesity. J Clin Pharmacol. 1983. PMID 6415130 Illustrations adapted from Servier Medical Art (smart.servier.com), CC BY 4.0. Structures drawn with RDKit.