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Applied Pharmacology 4, Half Life of Drugs

Understanding half life is important to inform how and when we administer any medication. These are not casual viewing, but are for serious students who want to understand the essential underpinning concepts of the care we give our patients. Notes Half life t 1/2 Pharmacokinetics and Pharmacodynamics Bioavailability – the proportion of an administered drug that reaches the systemic circulation in unchanged form Half life is the time from peak plasma concentration until half is eliminated Clearance T ½ First order kinetics First order elimination kinetics : "Elimination of a constant fraction per time unit of the drug quantity present. The elimination is proportional to the drug concentration." Zero-order elimination kinetics : The plasma concentration – time profile during the elimination phase is linear (Fig. 1). For example 20 mg are eliminated every hour, independently of the drug concentration in the body. Order 0 elimination is rather less common, mostly occurring when the elimination system is saturated. Eg. Alcohol Phenytoin Warfarin (Coumadin) Heparin Paracetamol (acetaminophen) Over dose of aspirin (normally t ½ = 3-4 hours) Steady state reached after 5 – 6 half lives (3.3 half lives for 90% concentrations), therefore possible loading dose. Drug eliminated after 5 half lives (95% eliminated after 4.5 half lives) Half life t ½ of common drugs Noradrenaline 2 minutes Salbutamol 1.6 hours Morphine 2 – 3 hours Methadone 24 hours Gentamycin 2 – 3 hours Penicillin 6 – 8 hours Diazepam 24 hours Fluoxetine 6 days Warfarin 4 days