Clarithromycin
Clarithromycin. 6-O-methyl erythromycin derivative — improved acid stability and tissue penetration. Strong CYP3A4 inhibitor (via 14-OH… Oral half-life 5 h.
6-O-methyl erythromycin derivative — improved acid stability and tissue penetration. Strong CYP3A4 inhibitor (via 14-OH metabolite); first-line DDI perpetrator in clinical pharmacology. H. pylori eradication regimens.
PK: zero-content on all four, and the intravenous row hung on an oral-only study. Re-sourced: F 0.52 from Chu 1992 (PMID:1387301), 22 healthy volunteers in a three-way crossover against an intravenous lactobionate infusion, verbatim "the mean absolute bioavailabilities of the two oral formulations were 52 and 55%"; half-life 5 h from PMID:9797791 at 500 mg twice daily. THE HALF-LIFE IS DOSE-DEPENDENT, NOT A CONSTANT: 2.3 to 6.0 h across 100 to 1200 mg, and 3.3 h at 250 mg. NO HUMAN VOLUME EXISTS in any abstract — the only intravenous steady-state volume found anywhere is in FOALS at 10.4 L/kg — so V 250 L is dropped without replacement. ACTIVE 14-HYDROXY METABOLITE: oral dosing yields markedly more of it than intravenous because of marked first-pass metabolism, so a scalar bioavailability on the parent understates oral antibacterial exposure. Kinetics are saturable and non-linear, so a linear rate constant is structurally wrong too. Four references were victim-drug studies in which this drug is the perpetrator and which state no clarithromycin parameter. INTERACTIONS: FOUR OF THE FIVE AFFINITIES INVERT THROUGH ONE ASSUMED CONCENTRATION OF 3 µM, and one note prints the arithmetic. THE ATORVASTATIN EDGE DOES NOT RECONSTRUCT and is left alone: its stored value implies a 3.5-fold rise against a cited lactone ratio of about 2.62, so it asserts a stronger interaction than its own source. Note the block shares its assumed concentration with erythromycin, which is a defensible modelling choice for two macrolides of similar exposure but is a CHOICE and not a measurement.
Pharmacokinetics
- Oral — t½ 5 h · F 52%
- IV — t½ 5 h · F 100%
Related compounds
- Simvastatin — contraindicated
- Tacrolimus — major
- Midazolam — major
- Triazolam — major
- Atorvastatin — warn
- Colchicine — contraindicated
Sources: PMID:9728893, PMID:9757151, PMID:21950641, PMID:23462027, PMID:1387301, PMID:9797791