What % of drug is eliminated by first order kinetics after four half-life cycles?
High-Yield Explanation
Ans. a (93.75 %). (Ref. KDT, Pharmacology, 4th ed., 53)Elimination of drugsZero order eliminationRate of elimination is constant regardless of C (i.e., constant amount of drug eliminated per unit time). Cp linearly with time. Examples of drugs--ethanol., phenytoin aspirin (at high or toxic concentrations).First order eliminationRate of elimination is proportional teo the drug concentration (i.e., constant fraction of drug eliminated per unit time). Cp exponentially with time. tl/2Drug eliminated1 t 1/2 50% drug is eliminated.2 t 1/2 75% (50 + 25) drug is eliminated.3 t 1/2 87.50% (50+ 25 + 12.50) drug is eliminated.4 t 1/2 93.75% (50+ 25 + 12.50 + 6.25) drug is eliminated.Thus, complete drug elimination occurs in 4-5 t ViVolume of distribution (apparent)Vd =Dose---C # Vd estimates the volume into which the drug has distributed (one needs to extrapolate plasma concentration at time zero)# The lower the Co, the higher the Vd, and vice versa# Drug stored in non fluid compartments like fat may have a Vd greater than TBW (e.g. lipid soluble drugs, quinacrine),# Drugs that bind strongly to plasma proteins have a Vd that approaches plasma volume.# Approximate Vd values (weight 70 kg)--plasma volume (3 L), blood (5L), extracellular fluid (12-14 L), TBW (40-42 L)Cdeg = Plasma concentration at time zeroClearanceCI =Rate of drug elimination----------------Plasma drug concentrationClearance is the theoretical volume of blood totally cleared of drug/unit time. It represents the ratio of drug elimination to its plasma concentration. For a drug with first-order elimination, clearance is constant. CI=Kc x Vd Kc=Elimination constant EliminationThe rate of elimination of the active drug. It is not drug excretion because it may be metabolized before excretion.