kinetics of drug elimination
-Plasma clearance
it is the volume of plasma from which all drug appears to be removed in a given time.clearance = rate of elimination (Roe) \C
-extraction ratio = C2/C1.
C1 is concentration of drug enters the kidneyC2 is concentration of drug exits the kidney
-Excretion rate =clearance * plasma concentration
mg/min ml/min mg/mlTotal body clearance
The total body (systemic) clearance, CLtotal or CLt, is the sum of the clearances from the various drug-metabolizing
and drug-eliminating organs.
CLt = CL hepatic + CL renal + CL pulmonary + CL other
CLt can be derived from the steady-state equation:
CLt = ke Vd
where ke = the first-order rate constant for drug elimination from the total body.
Vd is the volume of distribution
-half-life time t½
t½ =0.693Vd/CLThis is the period of time required for the concentration or amount of drug in the body to be reduced by one-half.
it depends on how quickly the drug is eliminated from the plasma.
drugs that are cleared from the blood more rapidly than others need to be given in regular doses to build up and maintain a high enough concentration in the blood to be therapeutically effective.
as repeated doses of a drug are administered its plasma concentration builds up and reaches what is known as a steady state. This is when the amount of drug in the plasma has built up to a concentration level that is therapeutically effective and as long as regular doses are administered to balance the amount of drug being cleared the drug will continue to be active. The time taken to reach the steady state is about five times the half life of a drug.
(a steady-state is achieved when the plasma concentration of drug remains constant)
Roe =CLt)(C)
Css ( the steady-state concentration) =Ro /keVd = RoCLt
Ro is the infusion rate
ke is the first-order elimination rate constant
Vd is the volume of distribution (constant for most drugs )
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