Rasagiline
Rasagiline. Selective irreversible MAO-B inhibitor for Parkinson disease (monotherapy in early disease or adjunct to levodopa). Propargylamine… Oral half-life 3 h.
Selective irreversible MAO-B inhibitor for Parkinson disease (monotherapy in early disease or adjunct to levodopa). Propargylamine class — same pharmacophore family as selegiline but no amphetamine-like metabolites (rasagiline metabolizes to 1-aminoindan, which is neuroprotective in some preclinical models — vs selegiline → methamphetamine + amphetamine). Once-daily 0.5-1 mg PO. CYP1A2 substrate (fluvoxamine + ciprofloxacin DDIs documented in label, but no abstract-verbatim AUC ratio per v1.1 GAPS). Selectivity for MAO-B is dose-dependent — at supratherapeutic doses loses selectivity, raises tyramine hypertensive crisis risk. PK (Azilect label, 1 mg PO qd SS): Cmax 2.5 ng/mL, Tmax 1 h, t½ 3 h SS, F 36%, Vss 87 L, protein binding 88-94%. Pharmacokinetics doesn't correlate with pharmacodynamics — irreversible MAO-B inhibition outlasts plasma exposure by weeks (target re-synthesis dictates effect duration). High-fat meal ↓Cmax 60%, ↓AUC 20%.
PK: THE ABSENCE OF AN EFFECT COMPARTMENT AND OF OCCUPANCY ROWS IS DELIBERATE AND CORRECT, AND IS RECORDED HERE SO NOBODY "COMPLETES" THE RECORD. Rasagiline is an IRREVERSIBLE MAO-B inhibitor: its plasma half-life is nearly irrelevant to its duration of effect, which is governed by enzyme resynthesis over weeks. A keo cannot represent that, and the reason stated in an earlier version of this note was WRONG and is corrected here: it is NOT that a linear filter must return to baseline as plasma clears — a filter terminal slope is min(ke, keo), so a slow enough keo would decay slowly. The real reasons are that a keo slow enough to reproduce weeks of effect would ALSO delay ONSET by the same rate, which is near-immediate here; that effect-site amplitude scales as keo/ke, so buying a slow decay collapses the signal into something ec50 would have to silently absorb; and decisively, that a linear filter has UNITY STEADY-STATE GAIN and therefore cannot ratchet, whereas irreversible inactivation accumulates across doses. A keo tuned to weeks would also wrongly delay ONSET, which is near-immediate. Positron emission tomography confirms the mechanism: "Gradual recovery toward the baseline state was observed in the weeks after termination of treatment ... compatible with the known rate of de novo synthesis of MAO-B, confirming the irreversible binding of rasagiline." CLASS 6 IS ACQUITTED — the stored volume is a steady-state figure computable only from intravenous data, and an absolute bioavailability requires an intravenous arm. A LIMITATION NOBODY HAD LOGGED: rasagiline is TIME-DEPENDENT, the mirror of carbamazepine autoinduction — "Overall systemic exposure was approximately theefold on day 7 versus day 1. The mean terminal elimination half-life (t1/2) was nearly doubled on day 7 compared to day 1." The stored half-life is the steady-state value; one parameter set cannot describe both states.
Pharmacokinetics
- Oral — t½ 3 h · F 36% · ka 2.683 h⁻¹ · Vd 87 L
Sources: PMID:29159774