Tolcapone
Tolcapone. Reversible nitrocatechol inhibitor of catechol-O-methyltransferase (COMT), acting both peripherally and — unlike entacapone — within… Oral half-life 1.8 h.
Reversible nitrocatechol inhibitor of catechol-O-methyltransferase (COMT), acting both peripherally and — unlike entacapone — within the CNS, which is why it is the COMT inhibitor used as a probe in prefrontal-dopamine and COMT Val158Met cognition research as well as a levodopa adjunct in Parkinson's disease. Erythrocyte COMT is inhibited by more than 80% at single oral doses of 200 mg and above. Carries a boxed warning for fulminant hepatic failure, so it is used with liver-enzyme monitoring.
PubChem CID 4659569 (C14H11NO5). PK: Jorga 1998 (PMID:9754991), sixteen healthy male volunteers, 200 mg oral vs 50 mg intravenous crossover — an ABSOLUTE bioavailability study. Verbatim: "The absolute bioavailability of an oral dose was approximately 60%", "resulting in a mean plasma half-life of 1.8 h", and "After an initial lag time of 0.5 h, tolcapone was rapidly absorbed". All three are stored. t½ cross-checks against the independent first-in-human study PMID:7768073: "Its mean elimination half-life was 2.0 +/- 0.8 hours (n = 42)". VOLUME AND CLEARANCE NOT STORED BECAUSE THEY ARE NOT READABLE: PubMed's indexed record of this abstract renders them as "the volume of distribution was approximately 9 1, and the total clearance was approximately 71.h-l" — OCR damage, present in the XML as well as the text rendering, and the three quantities as transcribed do not close (9 L at t½ 1.8 h implies 3.5 L/h, not 7). Guessing the intended units to recover a number would be transcription dressed as authoring. Logged in AUTHORING_GAPS.md; a full-text page-1 read unlocks both, and V would matter here because 35 L is the default that a 9 L central volume is nowhere near. ka NOT STORED either: the abstract says peaks were reached "within approximately 2 h" and that absorption followed "either zero- or first-order" kinetics, which is a bound and a hedge rather than a stated Tmax. PD: PMID:7768073 verbatim "At doses of 200 mg and higher, COMT activity was inhibited by more than 80%" — informational; no Hill row authored, since erythrocyte enzyme inhibition is not receptor occupancy. Dose range is the marketed 100 mg and 200 mg three-times-daily strengths; the cited studies used single 200 mg (PMID:9754991) and ascending 5-800 mg (PMID:7768073) doses.
Pharmacokinetics
- Oral — t½ 1.8 h · F 60%
Sources: PMID:9754991, PMID:7768073