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Entacapone (Comtan)

Dopaminergicprescriptionoral · inferred

Peripheral catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa to extend levodopa half-life and reduce off-time. 200 mg PO with each L-DOPA dose, up to 8 times daily (max 1600 mg/day). Very short plasma half-life (~0.4-0.7h) but biphasic with a minor slower phase; net effect is prolonging levodopa's half-life from ~1.5h to ~2.5h. Oral bioavailability ~35%. Notable brownish-orange urine discoloration, diarrhea (sometimes delayed weeks), and rare hepatotoxicity (greater with related tolcapone).

Projected serum levels — 200 mg, custom (shown daily)

Entacapone (Comtan)
Entacapone (Comtan) modeled serum levels, 200 mg custom (shown daily) over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 12.5 25 37.5 50 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1

Maintenance schedule: 200 mg custom (shown daily) (oral).

Modeled steady state after ~1 days: peak ≈ 48.9 mg, trough ≈ 0.020 mg body load. Population-based estimate over 15 days for a 200 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Dopaminergic
Route modeled
Oral
Model confidence
inferred
Half-life
2 h
Common dose
200 mg
Suggested maximum
1.6k mg/day
Reference dose range
100–1.6k mg (single dose)
Suggested cadence
custom (shown daily)
Validated against
200 mg oral — Cmax 1 mg/L at 1 h

Documented interactions

  • danger
    CBD (Cannabidiol) + Entacapone (Comtan) CYP inhibition

    CBD (Cannabidiol) reversible_inhibitor of UGT1A9 predicted to change Entacapone (Comtan) AUC by ~3.33x

  • danger
    Levothyroxine (Synthroid) + Entacapone (Comtan) Protein binding

    Entacapone (Comtan) may displace Levothyroxine (Synthroid) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index; free concentration…

  • danger
    Tacrolimus (Prograf) + Entacapone (Comtan) Protein binding

    Entacapone (Comtan) may displace Tacrolimus (Prograf) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index; free concentration…

  • danger
    Warfarin (Coumadin) + Entacapone (Comtan) Protein binding

    Entacapone (Comtan) may displace Warfarin (Coumadin) from plasma protein binding sites, transiently raising free drug concentration. This drug has a narrow therapeutic index; free concentration…

  • warning
    Apigenin + Entacapone (Comtan) Protein binding

    Apigenin may displace Entacapone (Comtan) from plasma protein binding sites, transiently raising free drug concentration.

  • warning
    Aripiprazole (Abilify) + Entacapone (Comtan) Protein binding

    Entacapone (Comtan) may displace Aripiprazole (Abilify) from plasma protein binding sites, transiently raising free drug concentration.

Serum checks 157 modeled interaction pairings for entacapone (comtan) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. Pharmacokinetic-pharmacodynamic interaction between entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, and levodopa in healthy volunteers Keränen T et al. · Clinical Pharmacology & Therapeutics, 1994 DOI

    Seminal PK/PD study demonstrating entacapone prolongs levodopa half-life and increases AUC without altering Cmax, forming the rationale for adjunctive use.

  2. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations Rinne UK et al. · Neurology, 1998 DOI

    Pivotal trial showing entacapone 200 mg with each levodopa dose reduces off-time and increases on-time in fluctuating PD.

2 published studies referenced in the app, each with a plain-language summary.