Erythromycin

pharmacological · cardiovascular · digestive · immune-hematologic · Oral · IV · Transdermal

Erythromycin. Macrolide antibiotic — binds bacterial 50S ribosome blocking translocation. Strong CYP3A4 inhibitor + motilin receptor agonist… Oral half-life 2 h.

Macrolide antibiotic — binds bacterial 50S ribosome blocking translocation. Strong CYP3A4 inhibitor + motilin receptor agonist (gastric prokinesia). DDI source: rises statin levels, prolongs QT via co-administered CYP3A4 substrates.

PK: THE STORED HALF-LIFE WAS A DOSE IN GRAMS. The cited abstract states no half-life anywhere; its only 1.5 is "erythromycin stearate, 1.5 g", appearing three times. That paper is also unusable in principle for a generic oral row, because it compares a SALT (stearate, 1.5 g) against a PRODRUG ESTER (ethylsuccinate, 3.0 g) — two molecules at two doses — and it has no intravenous arm. Re-sourced to Hall 1982 (PMID:7107981), 6 normal volunteers dosed intravenously and as enteric-coated tablets: "The elimination half-life was 1.6 +/- 0.7 hours (mean +/- s.d.) after the intravenous dose and 2.0 +/- 0.7 hours after the oral dose" and "The systemic availability of erythromycin was 33.5 per cent". THE ROUTE SPLIT IS REAL HERE and is kept: the oral value is 25% longer in the same subjects, a mild flip-flop from the enteric coat. V 57.6 L is a true steady-state volume from PMID:3606934. HAZARD LOGGED: that paper protein-binding figures, 30.5% unbound in normals and 58.3% in cirrhotics, must never migrate into a bioavailability field. INTERACTIONS: FOUR OF THE FIVE INVERT THROUGH THE SAME 3 µM USED FOR CLARITHROMYCIN, and two of the notes state it. ONE RECONSTRUCTION IS WORTH RECORDING BECAUSE IT IDENTIFIES THE ARM: the simvastatin edge does not fit the 6.2-fold parent-drug ratio its note leads with, but fits the 3.9-fold SIMVASTATIN ACID ratio in the same sentence — so the author was calibrating to the active acid, which is the right species, and the note simply leads with the other number. THE MIDAZOLAM EDGE IS LEFT ALONE: it implies a 2.8-fold rise while its note offers only "more than fourfold" and a 54 percent clearance fall, neither of which produces the stored value.

Pharmacokinetics

• Oral — t½ 2 h · F 34% · Vd 57.6 L
• IV — t½ 1.6 h · F 100% · Vd 57.6 L

Related compounds

• Simvastatin — major
• Midazolam — major
• Triazolam — major
• Sildenafil — warn
• Alfentanil — major

Sources: PMID:9757151, PMID:11879258, PMID:2501060, PMID:7107981, PMID:3606934