Solifenacin
Solifenacin. Competitive muscarinic receptor antagonist (M3-preferring) for overactive bladder — reduces detrusor overactivity. Hepatic CYP3A4… Oral half-life 2.8 d.
Competitive muscarinic receptor antagonist (M3-preferring) for overactive bladder — reduces detrusor overactivity. Hepatic CYP3A4 metabolism.
PK from FDA prescribing information (DailyMed setid 1d8e8f6f-0a59-479f-8415-c5c5f19e1977): absolute bioavailability ~90% (F 0.9), steady-state Vd ~600 L, terminal t½ ~45–68 h, Tmax 3–8 h, CYP3A4. ka_hr 0.85 derived from Tmax ~5 h (ke from t½ 55 h). PK: THE LABEL ROW HAD A PRIMARY IT WAS PARAPHRASING, AND THE OUTLIER-LOOKING NUMBERS ARE REAL. A ten-milligram oral versus five-milligram INTRAVENOUS crossover states them verbatim: "a high absolute bioavailability of 88.0% ... low clearance (9.39 L/h), and an extensive mean volume of distribution at steady state (599L)". Because that volume is a steady-state figure from a real intravenous dose, CLASS 6 IS REVERSED — the pairing is correct. The half-life of 55 h was the exact MIDPOINT of the label 45-68 h band; the only verbatim single healthy-subject mean anywhere is 68.2, from the control arm of an impairment study in six subjects, and its own inconsistency is recorded rather than hidden: 68.2 h beside 599 L and 9.39 L/h does not close under one compartment, because 599 is a steady-state volume while 68.2 is a TERMINAL half-life belonging to a larger one. ka 0.85 is a back-derivation to a round 5 h. THE BLADDER-EQUILIBRIUM QUESTION IS ANSWERED, NOT ASSUMED: this drug was given intravenously, works at 88% bioavailability, and produces effects at remote sites in the same subjects, so it is not loperamide-shaped. PK: THE ABSENT ABSORPTION RATE IS ACQUITTED AGAINST THE VESICARE LABEL. With no ka the solver substitutes 1.0/h and renders a peak at 4.6 h, and the label states "After oral administration of VESIcare to healthy volunteers, peak plasma levels (C max ) of solifenacin are reached within 3 to 8 hours after administration" (DailyMed setid 100678f1-313a-4e99-ae77-319c610a830f) — SO THE DEFAULT FALLS INSIDE THE PUBLISHED RANGE. Nothing is authored: storing a number would assert a measurement where the honest description is that the default happens to land correctly. Recorded because this record sits in a class where the same default is badly wrong for its neighbours, and a reader deserves to know which case this is.
Pharmacokinetics
- Oral — t½ 2.8 d · F 88% · Vd 599 L
Sources: PMID:12122494, PMID:15293866, PMID:17251687, PMID:15906588