Moxifloxacin, metabolism

Moxifloxacin - Moxifloxacin is well absorbed from the Gl tract. The C ax attained 1 to 3 hours after oral dosing. Steady state is achieved after 3 days or more. Moxifloxacin is widely distributed throughout the body. Moxifloxacin is metabolized via glucuronide and sulfate conjugation. 

Scheme 14.5 Metabolism of moxifloxacin in humans after a single dose (400 mg, p.o. or i.v.).

With regard to drug interactions, it is important to note that the cytochrome P-450 system is not involved in the metabolism of moxifloxacin. In vitro studies using cytochrome P-450 enzymes have shown that moxifloxacin does not inhibit the enzymes CYP 1A2, CYP 3A4, CYP 2C9, CYP 2C19, and CYP 2D6. Moxifloxa-cin s metabolic profile makes it highly unlikely that it will alter the pharmocoki-netics of drugs affected by these enzymes. In rhesus monkeys, oxidative phase I biotransformations do play an additional role, however [272,273]. 

Stass H, Kern A. Moxifloxacin - review of clinical pharmacokinetics metabolism and excretion. In 6th International Symposium on New Quinolones Abstract No. 132. Denver, Colorado, 1998. 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

Cardiovascular The effect of nelfinavir on the QT interval has been evaluated in a randomized, foiu -way crossover, third-party-blinded study in 68 healthy subjects with moxifloxacin as a positive control. Nelfinavir had no effect on the QT or QT intervals or the RR interval, even in poor metabolizers of CYP2C19, in whom exposure was high [189 ]. 

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