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Evaluation of Salicylic Acid's Volume of Distribution and Drug Equilibrium Distribution Ratios

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corbin
4 diapositives · 174 Views · Oct 21, 2014

This analysis evaluates the validity of three statements related to the pharmacokinetics of salicylic acid and its volume of distribution (Vd). Statement 1 is false, as the Vd does not indicate the physical volume of the extracellular fluid, and not all the drug is confined there. Statement 2 is true, confirming that the Vd must be at least 75L based on the liver's distribution ratio. Statement 3 is also true; despite a Vd of 200L, rapid equilibrium indicates that the drug primarily distributes into highly perfused organs.

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Evaluation of Salicylic Acid's Volume of Distribution and Drug Equilibrium Distribution Ratios
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  1. Assignment 4

  2. Briefly comment on the validity of each of the following statements: Statement 1: The volume of distribution of salicylic acid is 9-12 litres in man in the usual antipyretic dose of 600mg. Therefore, the extracellular fluids contain virtually all the drug in the body. [FALSE] - Assume it is a 70kg man, the extracellular fluids volume (ECF volume) will be approx 14 L. - At first glance  May appear that virtually all the drug is in the ECF. - HOWEVER, this may not be accurate because  Vd does not represent a physical volume of any compartment. Definition: (Vd of a drug is the fluid volume in which a drug seems to be distributed to account for its plasma concentration.) - In conclusion, differential binding of drug to plasma proteins and tissue proteins could have accounted for this experimentally determined volume (9-12L).  All the drug is not confined to ECF only.

  3. Statement 2: The equilibrium distribution ratio for a drug between the liver and plasma is 50:1. Since the volume of the liver is 2.3% of body weight, Vd of the drug must be at least 75L (assume 70kg man). [TRUE] Vd = Vp + V liver . K liver = 3L + [(2.3/60).42] . 50/1 = 83.5L Vd of the drug is 83.5L (>75L) which agrees with the statement that Vd of the drug must be at least 75L.

  4. Statement 3: A drug reaches distribution equilibrium within 30 minutes (note consider short time), yet whose Vd is 200L, must distribute primarily into highly perfused organs. [TRUE] Time  30 mins (short) Vd  200L (High Vd) According to equation (Vd = Vp + V T1 . K P1 + V T2 . K P2 + …), it can be derived that Kp must be high, as Vp is only 3L. Hence 197L (200L – 3L) must be accounted for by the apparent volume of organs. Now looking at the equation: Time to convey to tissue the amount at equilibrium = Kp/(Q/VT) Since time is small and numerator (Kp) is large, it can be derived that Q/VT(perfusion rate) must be very large comparative to Kp in order to give a short time. Hence, since Q/VT is large, it validates the statement that the drug must distribute primarily into highly perfused organs.