Entacapone pharmacokinetics are linear over the dose range of 5 mg to 800 mg, and are independent of levodopa and carbidopa coadministration. The elimination of entacapone is biphasic, with an elimination half-life of 0.4 h to 0.7 h based on the β-phase and 2.4 h based on the γ-phase. The γ-phase accounts for approximately 10% of the total AUC. The total body clearance after intravenous administration is 850 mL per min. After a single 200 mg dose of Entacapone Tablets, the Cmax is approximately 1.2 mcg per mL.

Absorption: Entacapone is rapidly absorbed, with a Tmax of approximately 1 hour. The absolute bioavailability following oral administration is 35%. Food does not affect the pharmacokinetics of entacapone.

Distribution: The volume of distribution of entacapone at steady state after intravenous injection is small (20 L). Entacapone does not distribute widely into tissues due to its high plasma protein binding. Based on in vitro studies, the plasma protein binding of entacapone is 98% over the concentration range of 0.4 mcg per mL to 50 mcg per mL. Entacapone binds mainly to serum albumin.

Metabolism and Elimination: Entacapone is almost completely metabolized prior to excretion, with only a very small amount (0.2% of dose) found unchanged in urine. The main metabolic pathway is isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer; the glucuronide conjugate is inactive. After oral administration of a 14C-labeled dose of entacapone, 10% of labeled parent and metabolite is excreted in urine and 90% in feces.

Special Populations: Entacapone pharmacokinetics are independent of age. No formal gender studies have been conducted. Racial representation in clinical trials was largely limited to Caucasians (there were only 4 blacks in one US trial and no Asians in any of the clinical trials); no conclusions can therefore be reached about the effect of entacapone on groups other than Caucasian.

Hepatic Impairment: A single 200 mg dose of entacapone, without levodopa and dopa decarboxylase inhibitor coadministration, showed approximately twofold higher AUC and Cmax values in patients with a history of alcoholism and hepatic impairment (n=10) compared to normal subjects (n=10). All patients had biopsy-proven liver cirrhosis caused by alcohol. According to Child-Pugh grading 7 patients with liver disease had mild hepatic impairment and 3 patients had moderate hepatic impairment. As only about 10% of the entacapone dose is excreted in urine as parent compound and conjugated glucuronide, biliary excretion appears to be the major route of excretion of this drug. Consequently, entacapone should be administered with care to patients with biliary obstruction.

Renal Impairment: The pharmacokinetics of entacapone have been investigated after a single 200 mg entacapone dose, without levodopa and dopa decarboxylase inhibitor coadministration, in a specific renal impairment study. There were three groups: normal subjects (n=7; creatinine clearance greater than 1.12 mL per sec per 1.73 m2), moderate impairment (n=10; creatinine clearance ranging from 0.60 mL per sec per 1.73 m2 to 0.89 mL per sec per 1.73 m2), and severe impairment (n=7; creatinine clearance ranging from 0.20 mL per sec per 1.73 m2 to 0.44 mL per sec per 1.73 m2). No important effects of renal function on the pharmacokinetics of entacapone were found.

Drug Interactions: See &PRECAUTIONS, Drug Interactions.