Buprenorphine
Buprenorphine. Partial µ-opioid agonist with high receptor affinity → displaces full agonists like heroin / fentanyl, producing withdrawal… Sublingual half-life 42 h.
Partial µ-opioid agonist with high receptor affinity → displaces full agonists like heroin / fentanyl, producing withdrawal if given too early. Ceiling effect on respiratory depression above ~32 mg — major safety advantage for OUD treatment. κ-antagonism may contribute to antidepressant / anti-anhedonia effects. Suboxone formulation adds naloxone to deter IV misuse.
PK: THE 17-HOUR TRANSDERMAL LAG IS THE CLONIDINE DEFECT REPEATING and is deleted. It appears in no buprenorphine transdermal abstract, and the published structural model says the opposite: "The final transdermal absorption model employed a zero-order input rate ... BUCCAL absorption was a first-order process with a time lag" — the lag belongs to a different route. The only use of the word for the patch is pharmacodynamic, "a long lag period for DOSE STABILISATION". The rest of the patch parameterisation is kept: 168 h is the stated wear interval and the input genuinely is zero-order, declining over the wear and stopping at removal. The stored 30 and 38.1 h half-lives were both unsourced, and the split was real in kind but for the wrong reason — terminal half-life IS route-dependent here because of an oral-mucosal depot and patch-limited input, so one disposition value of 42 h is now shared and the route effects left to the input model. SUBLINGUAL LOSS IS LARGE AND MEASURED: "Buprenorphine recovered from saliva ... was, on average, 52% to 55% of dose", causing "an almost twofold overestimation of bioavailability". No human volume exists in any abstract. A reference with NO ABSTRACT AT ALL is removed. THE EFFECT-COMPARTMENT VALUE IS KEPT BUT FLAGGED INCOMPLETE: its own paper states hysteresis is "a combination of biophase distribution kinetics AND receptor association/dissociation kinetics", with a partial-agonist ceiling, so a lone equilibration rate under-predicts both duration and ceiling.
Pharmacokinetics
- Sublingual — t½ 42 h · F 29%
- IV — t½ 42 h · F 100%
- Transdermal — t½ 42 h · F 14%
Sources: PMID:15966752, PMID:9048270, PMID:9684393, PMID:26865472