Doxorubicin
Doxorubicin. Anthracycline antineoplastic — DNA intercalation + topoisomerase II poisoning + iron-mediated ROS generation. Workhorse of breast /… IV half-life 13 h.
Anthracycline antineoplastic — DNA intercalation + topoisomerase II poisoning + iron-mediated ROS generation. Workhorse of breast / lymphoma / sarcoma regimens. Cumulative-dose cardiomyopathy is the dose-limiting toxicity (lifetime ceiling ~450 mg/m²).
PK: TWO ERRORS THAT WERE HIDING EACH OTHER, WHICH IS WHY EITHER ONE ALONE MAKES THE RECORD WORSE. The dose block was expressed per square metre in every source — and this record OWN mechanism text says so, quoting a lifetime ceiling in those units — so at the reference body surface the stored figures were 1.73-fold low. Independently, the volume is a steady-state one and, married to a terminal half-life, asserted a clearance 2.13-fold below a verbatim absolute figure, corroborated two ways. THE MODEL EXPOSURE WAS THEREFORE ONLY A QUARTER HIGH; CORRECTING THE DOSE ALONE WOULD HAVE MADE IT TWICE HIGH. Both move together: the doses become their body-surface equivalents and the half-life becomes a verbatim value from a normal-hepatic-function cohort, which brings the implied clearance within eight percent of the verbatim absolute. The abandoned half-life is itself verbatim but is the THIRD phase of a triexponential ("successive half-lives ... about 5 minutes, 1 hour and 30 hours"), carrying little exposure and, at three-weekly dosing, no accumulation. THE OBVIOUS TWO-COMPARTMENT ALTERNATIVE WAS TESTED AND REJECTED: one paper looks like a ready-made verbatim parameter set and the solver would accept it, but its microconstants are irreconcilable with its OWN reported clearance and exposure by a factor of nineteen and fail the standard consistency relation, while its clearance and exposure reproduce each other to two percent — so the microconstants are the broken half. DOSE: THE STORED FIGURE WAS THE RAW PER-WEIGHT NUMBER, NOT A DOSE — 30–90 mg/m² at 1.73 m², entered as flat milligrams. The dose unit enumeration has no weight-based member and the solver never weight-scales a dose, so THE ONLY REPRESENTABLE FORM IS THE SEVENTY-KILOGRAM EQUIVALENT, and that is what this record now carries. I TESTED THE OBJECTION THAT THIS READS A SCHEMA GAP AS A DATA DEFECT AND THE DISTINCTION IS CLEAN: vancomycin stores the seventy-kilogram equivalent of its weight-based regimen and is CORRECT, meropenem is genuinely flat-dosed and is CORRECT, and eleven records store the raw per-weight number and are WRONG BY ROUGHLY SEVENTY-FOLD. Both of my priors on the two correct records were wrong.
Pharmacokinetics
- IV — t½ 13 h · F 100% · Vd 1050 L
Sources: PMID:8137342