Table 11

Comparison of main properties and treatment strategies for entacapone and tolcapone

EntacaponeTolcapone
Oral bioavailability∼35%∼60%
Duration of action (effect of COMT activity in human erythrocytes)ShortLong
MetabolismAbundantAbundant
Brain penetrationNegligibleMarked
Ultimate goal of the therapyTransient intestinal COMT inhibition whilel-dopa is presentContinuous COMT inhibition in the whole body
Method of useMust be given with each dose of levodopa; between the doses COMT activity will recoverGiven every 6 h t.i.d., independently of levodopa dosing to keep COMT continuously suppressed; 12-h break at night
Combination tabletPossibleNot feasible
Goals of further developmentBetter absorptionProlonged duration of action
Means to achieve that goalWell-soluble and well-absorbed prodrug that rapidly releases entacapone?Well-absorbed prodrug that slowly releases tolcapone?