Tramadol
Tramadol. Weak µ-opioid agonist via CYP2D6-mediated conversion to O-desmethyltramadol (active metabolite with 200× µ-affinity vs parent). Parent… Oral half-life 5.5 h.
Weak µ-opioid agonist via CYP2D6-mediated conversion to O-desmethyltramadol (active metabolite with 200× µ-affinity vs parent). Parent compound is a serotonin + norepinephrine reuptake inhibitor — serotonergic load creates seizure + serotonin-syndrome risk. CYP2D6 polymorphism drives analgesia + respiratory depression variability.
PK: F 0.706 is verbatim and stands, but it is FORMULATION-SPECIFIC — oral drops without ethanol. The half-life 5.5 h is real yet belonged to PMID:9638309, which also gives the intravenous value as 5.2 h and the only true volume, "216 +/- 21 l (Vd,beta)". ANALYTE CAVEAT THAT CHANGES THE MEANING OF F: every stored value describes PARENT tramadol, while the opioid activity is carried by the CYP2D6-dependent O-desmethyl metabolite. So 0.706 is defensible only as the fraction reaching the circulation as parent, and is not a bioavailability of effect; in poor metabolisers parent exposure is unchanged or higher while the active metabolite collapses. ka 2 is dropped even though a real value exists, because absorption rate here is strongly formulation-dependent — absorption half-lives of 0.23, 0.34 and 0.38 h across three oral forms of the same drug — and every published figure comes bundled with a lag time this schema cannot represent, so a bare rate would predict onset too early.
Pharmacokinetics
- Oral — t½ 5.5 h · F 71% · Vd 216 L
- IV — t½ 5.2 h · F 100% · Vd 216 L
Sources: PMID:15509185, PMID:9638309