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Zero-Order Kinetics

Bible DictionaryPharmacology Glossary
Mechanisms of chemical reaction in which the reaction velocity is apparently independent of the concentration of all the reactants. Typically, in biological systems, one reactant (X) is present in a concentration greatly exceeding that of the other (Y), but is capable of undergoing change, while the concentration of Y, in contrast, does not undergo substantial change during the course of the reaction. For example, consider the inactivation of a drug (X), present in the body in an overwhelming quantity, by an enzyme (Y) present in a limited concentration in cells and having a specific maximum capacity to inactivate X. A sufficiently high concentration of X would "saturate" Y and make the system operate at, effectively, its maximum velocity; the amount of X inactivated per unit time would be constant and would depend on the maximum velocity per mass of Y and the total amount of Y present in the body; modest changes in concentration of X would not detectably change the velocity of the system operating at virtually its maximum rate. (Recollect the shape of the velocity - substrate concentration curve.) The reaction velocity would be independent of the concentrations of both X and Y. Eventually, the concentration of X would decrease to the point that it did not saturate Y, and the inactivation would proceed according to first-order kinetics. For a zero-order reaction, the plot of C (not ln or log C) against t yields a straight line: C = C0 - b0t, in which the slope (b0) is in units of concentration per unit time. The amount of change in concentration per unit time is constant; in the case of first-order kinetics, the fractional change in concentration per unit time is constant. Following administration of a drug eliminated by zero-order kinetics, the linear plot of C against t can be used to infer C0 and C and (if the dose is known) Vd, but no half-life (t1/2) can be determined. The elegant properties of multiple dose regimens (q.v.) for drugs eliminated according to first-order kinetics do not obtain for drugs eliminated by zero-order kinetics: Cmax for "zero-order drugs"does not approach Css,max as an asymptote; for zero-order drugs, Cmax increases progressively without limit with each dose, when equal doses are administered at equal intervals. Drugs which obey first-order kinetics with low doses may obey zero-order kinetics with large doses.Cf. First-Order KineticsHalf-Life

 

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