Varenicline
Varenicline. Partial agonist at α4β2 nicotinic ACh receptor — reduces cigarette craving + withdrawal while blocking the reinforcing effect of… Oral half-life 24 h.
Partial agonist at α4β2 nicotinic ACh receptor — reduces cigarette craving + withdrawal while blocking the reinforcing effect of smoked nicotine. Most efficacious smoking-cessation agent in head-to-head trials. Neuropsychiatric concerns (FDA black-box removed 2016 after EAGLES trial).
PK: I PREDICTED THIS WOULD BE THE SIMPLE ONE AND THAT ITS VALUES WERE PROBABLY CORRECT. The half-life is - 24 h is verbatim in three independent sources, with a Chinese cohort at 15.2 and 18.3 h recorded as counter-evidence. The bioavailability is not: F 0.9 IS A URINARY EXCRETION FRACTION, taken from "approximately 90% of the drug is excreted in the urine unchanged", where the same abstract actual availability statement is unquantified - "Varenicline is almost entirely absorbed following oral administration" - and a disposition study gives the human figure as 81%, again excreted unchanged rather than absorbed. No abstract states an absolute F for varenicline, so it is pinned to 1, which is also what the retained volume requires. ka 0.7 becomes the first measured absorption constant in this batch, from a population fit over 1878 smokers in nine pooled studies: "K(a), 1.69 h(-1) (1.27, 2.00)", with a 0.43 h lag the solver cannot yet express. V 415 is DISCLOSED AS A SUM rather than a quotation - it is that fit V(2)/F 337 L plus V(3)/F 78.1 L - and since every parameter in that model is apparent, pinning F to 1 also removes a genuine double-division. Its low protein binding is confirmed verbatim, "low (< or = 20%) and independent of age and renal function".
Pharmacokinetics
- Oral — t½ 24 h · F 100% · ka 1.69 h⁻¹ · Vd 415 L
Sources: PMID:19583451, PMID:16766716, PMID:22550286, PMID:21053991, PMID:19916991