Drug Elimination

  • Elavarasi Pichai
  • Mageshwaran Lakshmanan


The process by which the drug and/or its metabolite(s) are transferred permanently from the internal to the external environment is called excretion of the drug. The major route of drug elimination is kidney, followed by the liver, lungs, skin, salivary glands, mammary glands, and semen constituting the nonrenal pathways for drug elimination. Size, solubility, polarity, and protein binding nature are the major determinants for the elimination of drugs by the organ. The kinetics of elimination defines the half-life of the drug and thereby determines the dosing frequency of the drug. The drug can undergo linear (first order) kinetics or nonlinear (zero order or saturation) kinetics. Elimination is one of the sites for “drug interaction” wherein two drugs can compete for excretion resulting in toxicity or failure of therapy. Elimination of drugs in breast milk is a major concern while prescribing the drug for lactating mother. In clinics, the knowledge about the drug elimination gains significance in multidrug therapy, in the presence of organ failure and other co-morbid conditions.


Renal drug elimination Nonrenal drug elimination Clearance Half-life First-order kinetics Zero order kinetics 


  1. Gerk PM, Kuhn RJ, Desai NS, McNamara PJ (2001) Active transport of nitrofurantoin into human milk. Pharmacotherapy 21:669–675CrossRefGoogle Scholar
  2. Hellerstein S, Alon U, Warady BA (1992) Creatinine for estimation of glomerular filtration rate. Pediatr Nephrol 6:507–511CrossRefGoogle Scholar
  3. Schumann L, Wüstenberg PW, Hortian B, Kühnle HF (1993) Determination of glomerular filtration rate (GFR) on two consecutive days using inulin in a single-sample plasma clearance method. Clin Nephrol 39:65–69PubMedGoogle Scholar
  4. Hudson M, Stuchinskaya T, Ramma S, Patel J, Sievers C, Goetz S et al (2019) Drug screening using the sweat of a fingerprint: lateral flow detection of Δ9-tetrahydrocannabinol, cocaine, opiates and amphetamine. J Anal Toxicol 43(2):88–95. Scholar
  5. Pichini S, Zuccaro P, Pacifici R (1994) Drugs in semen. Clin Pharmacokinet 26:356–373CrossRefGoogle Scholar
  6. Miller DS, Pritchard JB (1997) Dual pathways for organic anion secretion in renal proximal tubule. J Exp Zool 279:462–470CrossRefGoogle Scholar
  7. Duggan DE, Hooke KF, Noll RM, Kwan KC (1975) Enterohepatic circulation of indomethacin and its role in intestinal irritation. Biochem Pharmacol 24:1749–1754CrossRefGoogle Scholar
  8. Duggan DE, Kwan KC (1979) Enterohepatic recirculation of drugs as a determinant of therapeutic ratio. Drug Metab Rev 9:21–41CrossRefGoogle Scholar
  9. Oh J, Chung H, Park S-I, Yi SJ, Jang K, Kim AH et al (2016) Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans. Diabetes Obes Metab 18:104–108CrossRefGoogle Scholar
  10. Maeda K, Tian Y, Fujita T, Ikeda Y, Kumagai Y, Kondo T et al (2014) Inhibitory effects of p-aminohippurate and probenecid on the renal clearance of adefovir and benzylpenicillin as probe drugs for organic anion transporter (OAT) 1 and OAT3 in humans. Eur J Pharm Sci 59:94–103CrossRefGoogle Scholar
  11. Ibrahim M, Garcia-Contreras L (2013) Mechanisms of absorption and elimination of drugs administered by inhalation. Ther Deliv 4:1027–1045CrossRefGoogle Scholar
  12. Elsby R, Chidlaw S, Outteridge S, Pickering S, Radcliffe A, Sullivan R et al (2017) Mechanistic in vitro studies confirm that inhibition of the renal apical efflux transporter multidrug and toxin extrusion (MATE) 1, and not altered absorption, underlies the increased metformin exposure observed in clinical interactions with cimetidine, trimethoprim or pyrimethamine. Pharmacol Res Perspect 5(5). Scholar
  13. Pérez M, Real R, Mendoza G, Merino G, Prieto JG, Alvarez AI (2009) Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones. J Vet Pharmacol Ther 32(5):498–502CrossRefGoogle Scholar
  14. Ellefsen KN, Concheiro M, Pirard S, Gorelick DA, Huestis MA (2016) Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration. Forensic Sci Int 260:95–101CrossRefGoogle Scholar
  15. Moreira-Barros J, Huang K-G, Tsai T-H (2018) Pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia. Gynecol Minim Invasive Ther 7:44–45CrossRefGoogle Scholar
  16. Rennick BR (1972) Renal excretion of drugs: tubular transport and metabolism. Annu Rev Pharmacol 12:141–156CrossRefGoogle Scholar
  17. Huo X, Liu K (2018) Renal organic anion transporters in drug-drug interactions and diseases. Eur J Pharm Sci 112:8–19CrossRefGoogle Scholar
  18. Lepist E-I, Ray AS (2016) Renal transporter-mediated drug-drug interactions: are they clinically relevant? J Clin Pharmacol 56:S73–S81CrossRefGoogle Scholar
  19. Idkaidek N, Hamadi S, El-Assi M, Al-Shalalfeh A, Al-Ghazawi A (2018) Saliva versus plasma therapeutic drug monitoring of pregabalin in Jordanian patients. Drug Res (Stuttg) 68:596–600CrossRefGoogle Scholar
  20. Charehsaz M, Gürbay A, Aydin A, Sahin G (2014) Simple, fast and reliable liquid chromatographic and spectrophotometric methods for the determination of theophylline in urine, saliva and plasma samples. Iran J Pharm Res 13:431–439PubMedPubMedCentralGoogle Scholar
  21. You G (2002) Structure, function, and regulation of renal organic anion transporters. Med Res Rev 22:602–616CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Elavarasi Pichai
    • 1
  • Mageshwaran Lakshmanan
    • 1
  1. 1.Department of PharmacologyThanjavur Medical CollegeThanjavurIndia

Personalised recommendations