Cilostazol
Cilostazol. Selective phosphodiesterase 3 inhibitor — raises platelet + smooth muscle cAMP. Vasodilator + antiplatelet. Used for symptomatic… Oral half-life 11 h.
Selective phosphodiesterase 3 inhibitor — raises platelet + smooth muscle cAMP. Vasodilator + antiplatelet. Used for symptomatic relief of intermittent claudication. Contraindicated in heart failure (PDE3 inhibitors increase mortality in HFrEF).
PK: FLIP-FLOP, AND THE EVIDENCE WAS IN THE SAME JOURNAL SUPPLEMENT AS THE CITED PAPER. PMID:10702883, never referenced here, states "The oral pharmacokinetics of cilostazol and metabolites are absorption-rate limited ... suggest 'flip-flop' pharmacokinetics" and, decisively, "The t1/2z of cilostazol decreased from 15.5 hours after a tablet to 2.5 hours after an ethanolic solution". The stored 11 h is therefore an APPARENT, absorption-limited tablet value - the cited abstract calls it "The apparent elimination half-life" - and under flip-flop the stored ka 0.7 and ke 0.063 have their roles reversed. ka is removed rather than inverted. F 0.95 was not a measurement of anything: the abstract offers only the qualitative "indicating a low extraction ratio drug, and hence low probability of a significant first-pass effect", and a human absolute bioavailability CANNOT EXIST because cilostazol has no intravenous form - the only two absolute figures in the literature are in rats. F is pinned to 1 so that the volume, which the source names verbatim as "The apparent volume of distribution (Vz/F; 2.76 L/kg)", is not divided by an availability twice. The parent-only row understates activity: OPC-13015 is 4-7 times more potent at PDE3 and is not modelled.
Pharmacokinetics
- Oral — t½ 11 h · F 100% · Vd 193 L
Sources: PMID:10702882, PMID:12180353, PMID:10702884, PMID:10702883