Clinical Clinical Pharmacokinetics of Pharmacokinetics of

PhenobarbitalPhenobarbitalDr. Muslim SuardiDr. Muslim Suardi

Faculty of Pharmacy Faculty of Pharmacy University of Andalas University of Andalas

20201313

INITIAL DOSAGE INITIAL DOSAGE DETERMINATION METHODSDETERMINATION METHODS

• Pharmacokinetic Dosing Method

Pharmacokinetic Dosing Pharmacokinetic Dosing MethodMethod

Estimation of • Cl • Vd • t1/2 & ke

ProblemProblem

• GO is a 50-year-old, 75-kg (5 ft 10 in) male with tonic-clonic seizures who requires therapy with oral PHENO. He has normal liver and renal function. Suggest an initial PHENO dosage regimen designed to achieve a steady-state concentration equal to 20 µg/mL.

11. . Estimate Cl & Vd according Estimate Cl & Vd according to disease states present in to disease states present in

the patient.the patient.• The Cl for an older patient is 4 mL/h/kg. Using

this value, the estimated Cl would equal 0.3 L/h: Cl = 75 kg*4 mL/h/kg = 300 mL/h or 0.3 L/h.

• The estimated Vd would be 53 L: 75 kg*0.7 L/kg = 53 L.

•  

2. 2. Estimate t1/2 & keEstimate t1/2 & ke

• Once the correct Cl & Vd estimates are identified for the patient, they can be converted into the PHENO t1/2 & ke estimates using the following eq:

• t1/2 = (0.693*V)/Cl = (0.693*53L)/ 0.3 L/h = 122 h,

k = Cl/V = 0.3 L/h / 53 L = 0.0057 h−1.

3. 3. Compute Dosage RegimenCompute Dosage Regimen

• Oral PHENO tab will be prescribed to this patient (F=1).

• The dosage equation for oral PHENO is D = (Css*Cl *) / F = (20 mg/L*0.3 L/h*24h) / 1 = 144 mg Rounded to 120 every 24h

3. Continued3. Continued

• A SS trough PHENO Csr should be measured after SS is attained in 3–5 t1/2.

• Since the patient is expected to have a t1/2 equal to 122h, the PHENO Css could be obtained any time after 4 weeks of dosing (5t1/2= 5*122h = 610 h or 25 d).

3. Continued3. Continued

• PHENO Csr should also be measured if the patient experiences an exacerbation of their epilepsy, or if the patient develops potential signs of PHENO toxicity.

• 3. Compute dosage regimen.

3. Continued3. Continued

• Oral PHENO tablets will be prescribed to this patient (F=1).

• The dosage eq for oral PHENO is D = (Css Cl ) / F = (20 mg/L*0.3 L/h*24 h) / 1 ⋅ ⋅= 144 mg, rounded to 120 every 24 hours.

• A SS trough PHENO Csr should be measured after SS is attained in 3–5t1/2.

3. Continued3. Continued

• Since the patient is expected to have a half-life equal to 122h, the PHENO Css could be obtained any time after 4 weeks of dosing (5t1/2 = 5*122h = 610 h or 25 d).

• PHENO Csr should also be measured if the patient experiences an exacerbation of their epilepsy, or if the patient develops potential signs of PHENO toxicity.