Telithromycin
Telithromycin. First-in-class ketolide antibiotic — semi-synthetic erythromycin derivative for community-acquired respiratory infections. Strong… Oral half-life 9.8 h.
First-in-class ketolide antibiotic — semi-synthetic erythromycin derivative for community-acquired respiratory infections. Strong CYP3A4 inhibitor (more potent than clarithromycin) with predictable QT prolongation. Withdrawn from the US market 2007 after post-marketing reports of severe hepatotoxicity (including fulminant hepatic failure), transient visual disturbances (cycloplegia / diplopia), syncope, and myasthenia gravis exacerbation. Retained in the registry for historical reference and as the textbook example of "post-market signal forced withdrawal" alongside cerivastatin and rofecoxib. PK (Ketek label rev 12/2010, SS 800 mg PO qd × 7d in healthy adults, n=18): Cmax 2.27 ± 0.71 µg/mL, AUC(0-24) 12.5 ± 5.4 µg·h/mL, Tmax 1.0 h (range 0.5-3.0), t½ 9.81 ± 1.9 h, F 57%, Vd 2.9 L/kg IV (V/F derived ≈ 905 L; true V ≈ 516 L with F 0.57), protein binding 60-70%.
PK: half-life 9.81 h is REAL but belonged to a primary the record did not cite; its actual citation is a narrative review that says "approximately 10 hours" — a provenance defect rather than a value defect. F 0.57 is verbatim and is a genuine absolute bioavailability from a crossover against an intravenous infusion. V 516 L IS UNSOURCEABLE ANYWHERE: the review gives 2.9 L/kg after intravenous infusion, about 203 L, and 516 is neither that at any plausible weight nor the apparent volume derived from it. THIS RECORD IS THE LEGITIMATE VERSION OF THE PAIRING WE USUALLY FLAG: an intravenous-derived volume beside a measured absolute bioavailability is CORRECT, so only the number needed replacing. A trap inside that source is logged — "2.9" appears twice, as the volume in L/kg and as the initial half-life in hours. The stored half-life is also only one of two phases; a one-compartment model at 9.81 h misfits the first six hours, where a 2.87 h phase dominates. ka 1 dropped. Withdrawn from most markets for hepatotoxicity.
Pharmacokinetics
- Oral — t½ 9.8 h · F 57% · Vd 203 L
Sources: PMID:16122280, PMID:11120961, PMID:12476037