Procainamide is used for the treatment of ventricular tachyarrhythmia. Its thera

Question

Procainamide is used for the treatment of ventricular tachyarrhythmia. Its therapeutic range is 4 to 8 mg/ml. It is eliminated by urine excretion and also metabolized to N- acetylprocainamide. When a 750 mg dose is administered intravenously to a normal healthy subject, the combined elimination half life is 3h. If you know that the ratio between urine excretion and metabolism is 65%-35%, what are the rate constants for the two individual pathways? What is the combined rate constant? Assume that the apparent volume of distribution (V_d) is 140 1, and the 750 mg dose is given as a bolus injection. Give a sketch of the compartment model, and write out the system of differential equations that describe it Use the Laplace Transform to solve the system you put together in the previous question

Explanation / Answer

750 mg is 750 x 10-3/235 g /mol = 0.0032 mol

Half life is 3h means the concentration reduces to half in 3 h in the body

Assuming the reactions to be first order we have

t1/2 = ln2/k

k = ln2/t1/2

k = 0.693/3h

b) k = 0.231 h-1 or 6.41 x 10-5 sec-1 is the overall rate

This is the combined rate constant since the individual rates are 65% and 35%

k = k1 + k2

a) k1 = 0.65 x k = 0.65 x 6.41 x 10-5 sec-1 = 4.18 x 10-5 sec-1 rate for urine excretion

k2 = 0.35 x k = 0.35 x 6.41 x 10-5 sec-1 = 2.24 x 10-5 sec-1 rate for metabolism.

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