Why Many Drugs Show a Fast Fall, Then a Slow Fall | Two Compartments (Pharmacokinetic Models 6.2)

Why does the plasma concentration of many drugs first fall fast and then more slowly? Lesson 6.2 of our pharmacokinetic models module describes the two-compartment model, its two exponential terms and the terminal half-life. Digoxin shows the two phases, and the 6 to 8 hours of tissue distribution show why the time of a blood sample matters. Transcript, equations and practice questions: https://freefraction.com/lessons/6-2-... 0:00 From one to two compartments 0:47 The two-compartment model 1:25 Distribution and elimination phases 1:46 The two-exponential equation 2:32 The two slopes 3:04 What each phase means in the body 3:43 The terminal half-life 4:22 Digoxin 5:13 Time of the blood sample 5:51 Summary Sources Jelliffe RW. Some comments and suggestions concerning population pharmacokinetic modeling, especially of digoxin, and its relation to clinical therapy. Ther Drug Monit. 2012. PMID 22735674 Yim DS, Choi S. Predicting human pharmacokinetics from preclinical data: volume of distribution. Transl Clin Pharmacol. 2020. PMID 33425799 Toutain PL, Bousquet-Mélou A. Plasma terminal half-life. J Vet Pharmacol Ther. 2004. PMID 15601438 Benowitz NL, Meister W. Clinical pharmacokinetics of lignocaine. Clin Pharmacokinet. 1978. PMID 350470 Cheng JW, Charland SL, Shaw LM, et al. Is the volume of distribution of digoxin reduced in patients with renal dysfunction? Determining digoxin pharmacokinetics by fluorescence polarization immunoassay. Pharmacotherapy. 1997. PMID 9165563 Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacometrics Syst Pharmacol. 2013. PMID 23887688 Sahin S, Benet LZ. The operational multiple dosing half-life: a key to defining drug accumulation in patients and to designing extended release dosage forms. Pharm Res. 2008. PMID 19015955 Ochs HR, Greenblatt DJ, Bodem G, et al. Dose-independent pharmacokinetics of digoxin in humans. Am Heart J. 1978. PMID 358815 US Food and Drug Administration. LANOXIN (digoxin) injection, prescribing information. 2025. https://dailymed.nlm.nih.gov/dailymed... Iisalo E. Clinical pharmacokinetics of digoxin. Clin Pharmacokinet. 1977. PMID 322907 Kramer WG, Kolibash AJ, Lewis RP, et al. Pharmacokinetics of digoxin: relationship between response intensity and predicted compartmental drug levels in man. J Pharmacokinet Biopharm. 1979. PMID 458556 Mooradian AD. Digitalis. An update of clinical pharmacokinetics, therapeutic monitoring techniques and treatment recommendations. Clin Pharmacokinet. 1988. PMID 3052985 Kelly RA, Smith TW. Recognition and management of digitalis toxicity. Am J Cardiol. 1992. PMID 1626485 Illustrations adapted from Servier Medical Art (smart.servier.com), CC BY 4.0. Structures drawn with RDKit.