Hepatic Clearance Calculations

A. The fraction unbound (fu) of Drug X was found to be 0.79. The intrinsic hepatic clearance in humans was estimated at 259.9 mL/min. Typical hepatic blood flow in adults is 1.5 L/min. Based on the well-stirred model, calculate the extraction ratio and hepatic clearance.

Extraction ratio = 0.1204 No units
Hepatic Clearance = 180.6 ml/min

B. RJ is a patient with epilepsy. She has been taking Drug X, 2000 mg by mouth BID, to manage her seizures for several years. Assume that Drug X is only cleared by the liver. Calculate the steady-state total concentration (Css) and steady-state unbound concentration (Css,u). Use the simplified hepatic clearance equations for drugs with high (>0.7) or low extraction ratios (<0.3).

Concentration Steady State = 0.01353 mg/mL
Unbound Concentration Steady State = 0.01069 mg/mL

C. Recently, RJ was prescribed an antibiotic for a bacterial infection for 21 days. This antibiotic is known to decrease the protein binding of Drug X by 15%. Calculate the new Css and Css,u.

Fraction Unbound = 0.9085

Concentration Steady State = 0.01176 mg/mL
Unbound Concentration Steady State = 0.01068 mg/mL

D. Does the dosing regimen need to be adjusted for RJ due to the drug-drug interaction? Yes = 0 and No = 1.

Answer is NO = 1

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