Roflumilast
Roflumilast. Selective PDE4 inhibitor — anti-inflammatory effect on bronchial inflammation. Oral approval for severe COPD with chronic… Oral half-life 15 h.
Selective PDE4 inhibitor — anti-inflammatory effect on bronchial inflammation. Oral approval for severe COPD with chronic bronchitis. Weight loss + GI / psychiatric side effects limit use.
PK: zero-content on all four, and THE PARENT IS THE WRONG ANALYTE WHILE THE RECORD ALREADY KNEW IT — its own effect note says "the active N-oxide sustains inhibition" yet every stored value describes the parent. The N-oxide "accounts for >90% of roflumilast total PDE4 inhibitory activity", reaches about TWELVE-FOLD higher exposure, and accumulates 169% against the parent 20-40%, so the two analytes reach steady state differently. Worse, the 21% of an oral dose that fails the bioavailability is NOT LOST BUT CONVERTED to the active N-oxide, so applying a parent bioavailability DISCARDS ACTIVE DRUG — the structure is biased, not merely incomplete. The parent values are now correctly sourced from the intravenous study the record never cited, which is internally consistent, and the volume is intravenous-derived so the pairing with bioavailability is right. Absorption is first-order WITH A LAG and the metabolite forms zero-order, so ka 1 is dropped. THE EFFECT-COMPARTMENT VALUE IS REMOVED: it was invented and attached to the analyte carrying under a tenth of the activity, against a clinical benefit that accrues over weeks. A reference is an in-vitro leukocyte study with no kinetics.
Pharmacokinetics
- Oral — t½ 14.8 h · F 79% · Vd 204 L
Sources: PMID:27306372, PMID:21176727, PMID:22059647, PMID:20690782