Cyclophosphamide

pharmacological · digestive · immune-hematologic · Oral · IV

Cyclophosphamide. Nitrogen-mustard alkylating prodrug — CYP2B6 + CYP3A4 oxidation produces phosphoramide mustard (cytotoxic) + acrolein… Oral half-life 6.4 h.

Nitrogen-mustard alkylating prodrug — CYP2B6 + CYP3A4 oxidation produces phosphoramide mustard (cytotoxic) + acrolein (urotoxic — mesna co-administration prevents hemorrhagic cystitis). Used in lymphoma + breast + lupus + vasculitis regimens.

PK: the stored 4 h oral and 9 h intravenous half-lives were BOTH midpoints of ranges in the old citation (1.32-6.8 h and 5.97-12.37 h) and encoded a route-dependent disposition half-life, which cannot be right — the same paper own metabolite endpoint shows "no significant difference following oral and intravenous administration". A single value is now carried on both routes. V 46.5 L is Ahmed 2020 (PMID:32390827), 267 patients, verbatim "clearance and apparent volume of distribution of 5.41 L/h and 46.5 L", and the half-life follows from that fit ln2 x V/CL = 6.4 h rather than from a second paper; F is pinned to 1 because that volume is apparent. F 0.75 dropped: it was one minus a hepatic extraction ratio of 0.25, which ignores gut availability and is not a bioavailability. Analyte note: cyclophosphamide is a prodrug and these are parent values.

Pharmacokinetics

Sources: PMID:497087, PMID:32390827, PMID:3552204