Drug Clearance Calculator

Drug clearance (CL) is the theoretical volume of blood from which a drug is completely removed per unit of time (units: mL/min or L/hr). Total body clearance is the sum of all elimination routes: renal clearance + hepatic clearance + other clearance. A higher clearance means the drug is eliminated more quickly. Clearance is the primary pharmacokinetic parameter that determines steady-state drug concentration: Css = Dose rate / CL.

Volume of distribution (Vd) is not a real volume, but a theoretical volume that relates the total amount of drug in the body to its plasma concentration. Vd = Dose / C0, where C0 is the initial plasma concentration. A large Vd (greater than total body water, about 42 L for a 70 kg adult) means the drug distributes extensively into tissues. Highly lipophilic drugs like chloroquine can have Vd values of hundreds or thousands of litres.

The relationship is: t1/2 = (0.693 x Vd) / CL. This shows that half-life is not an independent parameter - it is determined by both Vd and CL. A drug can have a long half-life either because it has a large Vd (distributes widely into tissues) or because it has a low clearance (eliminated slowly). Understanding CL and Vd separately is more informative than half-life alone for predicting drug behaviour.

For drugs primarily eliminated by the kidneys, renal impairment reduces clearance proportionally to the reduction in GFR. If a drug is 100% renally cleared and GFR falls by 50%, clearance also falls by 50%, doubling the half-life. This means the drug accumulates to higher steady-state concentrations at the same dose. The Cockcroft-Gault creatinine clearance formula is the standard used for dose adjustment in renal impairment for most drugs.

Bioavailability (F) is the fraction of a dose that reaches the systemic circulation unchanged. Oral bioavailability is reduced by incomplete absorption and first-pass hepatic metabolism. Some drugs have very low bioavailability (e.g. morphine F = 30%, propranolol F = 26%) while others are nearly 100% (e.g. amoxicillin F = 95%). When calculating steady-state concentrations from oral dosing, the dose rate must be multiplied by F: Css = (F x Dose rate) / CL.