VPT 311: General and Systemic Veterinary Pharmacology (2+1)

IMPORTANT PHARMACOKINETIC PARAMETERS

Most important parameters

t_1/2, Cl_B, V_d, AUC

Half life (t_1/2) – Plasma half life – the time taken for the plasma concentration to be reduced to half its original value

• Elimination half life (t_{1/2 β} ) – the half life calculated from the elimination curve (log dose in y axis vs time )
• t_{1/2 b} = 0.693 / β ( elimination rate constant) (where β = slope of the curve x 2.303)
• Longer the half life longer is the duration of action
• At one t_1/2 – 50 % of drug is eliminated
• At two t_1/2 - 75% of drug is eliminated (50 + 50% of remaining 50)
• At three t_1/2 - 87.5% of drug is eliminated
• At 4 t_1/2 - 93.75 % of drug is eliminated

AUC = Area Under the concentration time Curve

• Calculated by the trapezoidal rule.
• Important in calculating bioavailability and other parameters

Volume of Distribution (V_d)

• It is defined as the amount of body fluid containing the drug - an apparent not an accurate value – the drug to be equally distributed in the whole body fluid.
• V_d = dose given / conc. of the drug in plasma
• For a more accurate description,
  • V_{d area} = Dose / β x AUC for i.v. (or) Dose x F / β x AUC for non i.v.
• V_d is indicative of extent of drug penetration.
• More distribution – greater V_d
• Highly protein bound and tissue bound drugs have higher V_d
• Drugs with higher V_d preferred for treatment in remote sites – skin, bone , muscle, etc.

Clearance – (Cl)

• Total body clearance (Cl_B) - An index of efficiency of drug elimination
• Defined as the volume of body fluid cleared of the drug per unit time
• For a given drug by the given route, Cl and V_d are characteristic and help in dose determination
• V _{d =} Cl / β