Moxifloxacin 100 mg · Tablets

Moxifloxacin hydrochloride is a member of the fluoroquinolone class of antibacterial agents [see Microbiology (12.4)].

Absorption — Moxifloxacin, given as an oral tablet, is well absorbed from the gastrointestinal tract. The absolute bioavailability of moxifloxacin is approximately 90 percent. Co-administration with a high fat meal (that is, 500 calories from fat) does not affect the absorption of moxifloxacin.

Consumption of 1 cup of yogurt with moxifloxacin does not affect the rate or extent of the systemic absorption (that is, area under the plasma concentration time curve (AUC).

Plasma concentrations increase proportionately with dose up to the highest dose tested (1200 mg single oral dose). The mean (± SD) elimination half-life from plasma is 12 ± 1.3 hours; steady-state is achieved after at least three days with a 400 mg once daily regimen.

Mean Steady-State Plasma Concentrations of Moxifloxacin Obtained With Once Daily Dosing of 400 mg Either Orally (n=10) or by Intravenous Infusion (n=12)

Distribution — Moxifloxacin is approximately 30 to 50% bound to serum proteins, independent of drug concentration. The volume of distribution of moxifloxacin ranges from 1.7 to 2.7 L/kg. Moxifloxacin is widely distributed throughout the body, with tissue concentrations often exceeding plasma concentrations. Moxifloxacin has been detected in the saliva, nasal and bronchial secretions, mucosa of the sinuses, skin blister fluid, subcutaneous tissue, skeletal muscle, and abdominal tissues and fluids following oral or intravenous administration of 400 mg. Moxifloxacin concentrations measured post-dose in various tissues and fluids following a 400 mg oral or intravenous dose are summarized in Table 9. The rates of elimination of moxifloxacin from tissues generally parallel the elimination from plasma.

Metabolism — Approximately 52% of an oral or intravenous dose of moxifloxacin is metabolized via glucuronide and sulfate conjugation. The cytochrome P450 system is not involved in moxifloxacin metabolism, and is not affected by moxifloxacin. The sulfate conjugate (M1) accounts for approximately 38% of the dose, and is eliminated primarily in the feces. Approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate (M2), which is excreted exclusively in the urine. Peak plasma concentrations of M2 are approximately 40% those of the parent drug, while plasma concentrations of M1 are generally less than 10% those of moxifloxacin.

In vitro studies with cytochrome (CYP) P450 enzymes indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2.

Excretion — Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces). A total of 96% ± 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean (± SD) apparent total body clearance and renal clearance are 12 ± 2 L/hr and 2.6 ± 0.5 L/hr, respectively.

Geriatric — Following oral administration of 400 mg moxifloxacin for 10 days in 16 elderly (8 male; 8 female) and 17 young (8 male; 9 female) healthy volunteers, there were no age-related changes in moxifloxacin pharmacokinetics. In 16 healthy male volunteers (8 young; 8 elderly) given a single 200 mg dose of oral moxifloxacin, the extent of systemic exposure (AUC and C max) was not statistically different between young and elderly males and elimination half-life was unchanged. No dosage adjustment is necessary based on age. In large phase III studies, the concentrations around the time of the end of the infusion in elderly patients following intravenous infusion of 400 mg were similar to those observed in young patients [see Use in Specific Populations (8.5)].

Gender — Following oral administration of 400 mg moxifloxacin daily for 10 days to 23 healthy males (19 to 75 years) and 24 healthy females (19 to 70 years), the mean AUC and C max were 8% and 16% higher, respectively, in females compared to males. There are no significant differences in moxifloxacin pharmacokinetics between male and female subjects when differences in body weight are taken into consideration.