Metabolism Site of Moxifloxacin
Moxifloxacin undergoes metabolism primarily through glucuronide and sulfate conjugation pathways, not through the hepatic cytochrome P450 system. 1
Primary Metabolic Pathways
Approximately 52% of an oral or intravenous dose of moxifloxacin is metabolized via two main conjugation reactions 1:
- Sulfate conjugation (M1 metabolite): Accounts for approximately 38% of the administered dose and is eliminated primarily in the feces 1
- Glucuronide conjugation (M2 metabolite): Accounts for approximately 14% of the dose and is excreted exclusively in the urine 1
Key Clinical Implications of Non-P450 Metabolism
The cytochrome P450 system is not involved in moxifloxacin metabolism, and moxifloxacin does not affect cytochrome P450 enzymes. 1, 2 This metabolic profile provides several important clinical advantages:
- Minimal drug-drug interactions: Unlike many antibiotics, moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2 1
- No dosage adjustment in hepatic disease: The clearance of moxifloxacin is not substantially altered in liver disease, allowing standard dosing in most patients with hepatic impairment 1, 3
- No dosage adjustment in renal disease: Standard 400 mg once daily dosing can be maintained even in patients with creatinine clearance <30 mL/min or those on hemodialysis 4
Excretion Profile
Approximately 45% of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces), with a total of 96% ± 4% of an oral dose excreted as either unchanged drug or known metabolites 1. The mean apparent total body clearance is 12 ± 2 L/hr, with renal clearance of 2.6 ± 0.5 L/hr 1.
Important Monitoring Caveat
Despite the lack of hepatic P450 metabolism, baseline liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) should still be obtained before initiating moxifloxacin 5. This is because moxifloxacin can cause idiosyncratic hepatotoxicity through mechanisms unrelated to its metabolism, potentially involving gut microbiome alterations and disruption of butyric acid production 6. Liver enzymes should be checked every 1-2 weeks for the first 2-3 months of therapy 5.