1. Clinical Pharmacokinetics of Procainamide Dr. Muslim Suardi Faculty of Pharmacy University of Andalas 2013

2. INITIAL DOSAGE DETERMINATION METHODS The pharmacokinetic dosing method Literature based recommended dosing

3. The Pharmacokinetic Dosing Method t 1/2 & ke estimate Vd estimate Selection of appropriate Pk model & equations Css selection

4. Problem LK is a 50yo, 75-kg (5 ft 10 in) male with ventricular tachycardia who requires therapy with oral PROC SR-tab. He has normal liver & cardiac function. Suggest an initial oral PROC dosage regimen designed to achieve a PROC Css equal to 4 µg/mL.

5. 1. Estimate t1/2 & ke according to disease states & conditions present in the patient The expected PROC t1/2 for an individual with normal hepatic & renal function is 3.3h. The ke is computed using the following formula: k = 0.693/t1/2 = 0.693/3.3 h = 0.210 h −1.

6. 2. Estimate Vd & Cl The patient is not obese, so the estimated PROC Vd will be based on ABW: V = 2.7 L/kg*75 kg = 203 L. Estimated PROC Cl is computed by taking the product of the Vd & ke: Cl=kV = 0.210 h −1 * 203L = 42.6 L/h

7. 3. Compute Dosage Regimen Oral SR PROC tab will be prescribed to this patient (F=0.83). Because the patient has a rapid PROC Cl & short t 1/2, initial τ will be set to 6h. The dosage equation for oral PROC is D = (Css*Cl*τ) / F = (4 mg/L*42.6L/h*6h) / 0.83 =1231mg, rounded to 1250 mg every 6h.

8. 3. Continued SS PROC & NAPA Csr could be measured after SS is attained in 3–5t 1/2. Since the patient is expected to have a t 1/2 equal to 3.3h for PROC & 6h for NAPA, the Css could be obtained any time after the first day of dosing (5 t 1/2 = 5*3.3 h = 16.5 h for PROC, 5 t 1/2 = 5*6h = 30 h for NAPA).

9. 3. Continued PROC & NAPA Csr should also be measured if the patient experiences a return of their arrhythmia, or if the patient develops potential signs or symptoms of PROC toxicity.