Elimination half-life The half-life is often determined from the plasma drug concentration curve shown here.The clearance(Cl)is the volume of fluid from which a drug is eliminated per unit of time.It can be calculated as the product of the volume of distribution,Vd,and ke.If 0.693/t1/2 is substituted for ke,the equation is as follows: Cl=0.693Vd/t12 Thus,a drug's clearance is directly proportional to its volume of distribution and is inversely proportional to its half-life. Disease,age,and other physiologic variables can alter drug clearance or volume of distribution and thereby change the elimination half-life. First-order kinetics Single-dose pharmacokinetics 8 First-order kinetics: Characteristic of passive diffusion(simple 2- diffusion along electrochemical gradient). 2 3 A Time (h) Zero-order kinetics Zero-order kinetics: Characteristic of active transport(with the 4 assistant of carriers,enzymes and plasma proteins).It takes energy and can be against 2 electrochemical gradient. 0 0 2 3 Time (h)Elimination half‐life • The half‐life is often determined from the plasma drug concentration curve shown here. The clearance (Cl) is the volume of fluid from which a drug is eliminated per unit of time. It can be calculated as the product of the volume of distribution, Vd, and ke. If 0.693/t1/2 is substituted for ke, the equation is as follows: Cl = 0.693 Vd/t1/2 • Thus, a drug's clearance is directly proportional to its volume of distribution and is inversely proportional to its half‐life. Disease, age, and other physiologic variables can alter drug clearance or volume of distribution and thereby change the elimination half‐life. First-order kinetics: Characteristic of passive diffusion (simple diffusion along electrochemical gradient). Single-dose pharmacokinetics Zero-order kinetics: Characteristic of active transport (with the assistant of carriers, enzymes and plasma proteins). It takes energy and can be against electrochemical gradient