Levaquin - Clinical Pharmacology

CLINICAL PHARMACOLOGY

The mean ±SD pharmacokinetic parameters of levofloxacin determined under single and steady-state conditions following oral (p. o.) or intra-venous (i. v.) doses of levofloxacin are summarized in Table 1.

Absorption

Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are usually attained one to two hours after oral dosing. The absolute bioavailability of a 500 mg tablet and a 750 mg tablet of levofloxacin are both approximately 99%, demonstrating complete oral absorption of levofloxacin.

Following a single intravenous dose of levofloxacin to healthy volunteers, the mean ±SD peak plasma concentration attained was 6.2 ±1.0 µg/ mL after a 500 mg dose infused over 60 minutes and 11.5 ±4.0 µg/ mL after a 750 mg dose infused over 90 minutes.

Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral or i. v. dosing regimens. Steady-state conditions are reached within 48 hours following a 500 mg or 750 mg once-daily dosage regimen. The mean ±SD peak and trough plasma concentra-tions attained following multiple once-daily oral dosage regimens were approximately 5.7 ±1.4 and 0.5 ±0.2 µg/ mL after the 500 mg doses, and 8.6 ±1.9 and 1.1 ±0.4 µg/ mL after the 750 mg doses, respectively. The mean ±SD peak and trough plasma concentrations attained following multiple once-daily i. v. regimens were approximately 6.4 ±0.8 and 0.6 ±0.2 µg/ mL after the 500 mg doses, and 12.1 ±4.1 and 1.3 ±0.71 µg/ mL after the 750 mg doses, respectively.

Oral administration of a 500-mg LEVAQUIN tablet with food slightly prolongs the time to peak concentration by approximately 1 hour and slightly decreases the peak concentration by approximately 14%. Therefore, levofloxacin tablets can be administered without regard to food. The plasma concentration profile of levofloxacin after i. v. administration is similar and comparable in extent of exposure (AUC) to that observed for levofloxacin tablets when equal doses (mg/ mg) are administered. Therefore, the oral and i. v. routes of administration can be considered interchangeable. (See following chart.)