Ticagrelor
Ticagrelor. Reversible P2Y12 ADP-receptor antagonist — direct-acting (not a prodrug) so onset within ~30 min independent of CYP2C19 phenotype.… Oral half-life 8 h.
Reversible P2Y12 ADP-receptor antagonist — direct-acting (not a prodrug) so onset within ~30 min independent of CYP2C19 phenotype. Used in ACS / post-PCI antiplatelet therapy. Dyspnea (~15%) from adenosine reuptake inhibition in lung.
PK: THE BEST AVAILABLE SOURCE IS A ONE-COMPARTMENT POPULATION MODEL — THIS REGISTRY OWN MODEL SHAPE — AND NOBODY HAD USED IT. Across nearly seven thousand patients: "A one-compartment model with population mean PK parameters of first-order absorption rate constant (0.67/h), apparent systemic clearance (14 L/h), and apparent volume of distribution (221 L) was shown to best describe the PK profile of ticagrelor." The absorption rate is therefore directly storable verbatim, replacing a value that was this catalog default and that predicted a peak at 2.68 h against a verbatim median of 1.3 to 2 h. CLASS 6 IS ACQUITTED: a 15 mg intravenous dose was given alongside the oral, so the stored volume is intravenous-anchored, and that same study carries the bioavailability verbatim — "The mean absolute bioavailability of ticagrelor was 36%" — which is the source that should have been cited. THE EFFECT COMPARTMENT IS THE LEGITIMATE CASE: unlike the irreversible inhibitors audited in a sibling group, ticagrelor is a REVERSIBLE P2Y12 antagonist, and its own literature says so — inhibition "was nearly complete at 2 h" and then "gradually decreasing with declining plasma concentration ... indicating that the IPA is reversible". A plasma-linked effect model is appropriate here, and the record already reflects it. ONE MISS IS RECORDED: an absorption lag, not the rate, explains a fourfold over-prediction at the earliest sampling time.
Pharmacokinetics
- Oral — t½ 8 h · F 36% · ka 0.67 h⁻¹ · Vd 88 L
Sources: PMID:25500486, PMID:19552634, PMID:30048515, PMID:21727045, PMID:27191766, PMID:27536453