Azithromycin
Azithromycin. Azalide macrolide — 50S ribosomal inhibitor; expanded gram-negative + atypical coverage vs erythromycin. Long tissue half-life… Oral half-life 2.9 d.
Azalide macrolide — 50S ribosomal inhibitor; expanded gram-negative + atypical coverage vs erythromycin. Long tissue half-life supports 5-day dosing. Modest CYP3A4 inhibition (less than erythromycin/clarithromycin). QT prolongation signal at high doses.
PK: the intravenous row carried the ORAL study half-life. THE 41 h IS A SAMPLING-WINDOW ARTEFACT, not a route difference: that study sampled to 120 h, while a 240-h study recovers 69 h, which is now stored for both routes. F corrected 0.38 to the stated 37%. V 2331 L is 33.3 L/kg, and it is REAL BUT NOT A DISTRIBUTION SPACE — its own source explains that "the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug". Tissue half-lives run 2.3 to 3.2 DAYS against a serum peak of 0.4 mg/L, so a serum-referenced volume for a drug that sits almost entirely outside serum is arithmetically correct and physiologically empty. EFFECT IS INTRACELLULAR AND DECOUPLED: efficacy is argued from tissue concentrations exceeding the minimum inhibitory concentration, not from serum. ka 0.5 dropped; oral input is degradation-competing rather than simply first-order. PK: ABSORPTION RATE AUTHORED FROM THE ZITHROMAX LABEL. This row carried no ka, so the solver substituted 1.0/h and put the peak at 4.6 h. Source, verbatim from the current FDA label (DailyMed setid db52b91e-79f7-4cc1-9564-f2eee8e31c45): "Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC 0–72 =4.3 (1.2) mcg∙hr/mL; C max =0.5 (0.2) mcg/mL; T max =2.2 (0.9) hours." A point value with its spread. PUBMED HAS THIS NOWHERE — 27 targeted searches across two passes returned four usable peak times for this whole class, because Tmax is a label figure that rarely reaches an abstract. A regulatory label is already a first-class source in this schema. With the stored half-life fixing ke, Tmax solves uniquely for ka by inverting the model own definition, ln(ka/ke)/(ka-ke) = Tmax — ARITHMETIC, NOT AN ESTIMATE — giving 2.522/h, which reproduces 2.2 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC, so only the shape moves.
Pharmacokinetics
- Oral — t½ 2.9 d · F 37% · ka 2.522 h⁻¹ · Vd 2331 L
- IV — t½ 2.9 d · F 100% · Vd 2331 L
Sources: PMID:8913468, PMID:2154441