Factors affecting the drug cone-time profile (Cont'd)

b- Volume of distribution :

Examine the drug conc-time profiles after iv administration of the same dose of different drugs that have the same total body clearance, and different Vd

Parameters
D (mg) CLΤ(L/hr) Vd (L)
1000 10 15
Volume (L)

Administration of the same dose of drugs that have different Vd and similar CLT, produces lower initial drug conc and slower rate of elimination in the drug with larger volume of distribution.

Example:

What is the iv bolus dose of each of the following antiarrhythmic drugs required to achieve plasma concentration of 5 mg/L immediately after administration (Disopyramide Vd =1.7 L/kg, lidocaine Vd =1.3 L/kg, procainamide Vd = 2 L/kg, and quinidine = 3 L/kg)

Disopyramide = 5 mg x 1.7 L/kg = 8.5 mg/kg
Lidocaine = 5 mg x 1.3 L/kg = 6.5 mg/kg
Procainamide = 5 mg x 2 .0 L/kg =10 mg/kg
Quinidine = 5 mg x 3.0 L/kg =15 mg/kg
Dose = Cp . Vd
Drugs with larger Vd require larger doses to achieve the same initial concentration.
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