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 levofloxacin from a 500 mg tablet and a 750 mg tablet of LEVAQUIN® are both approximately 99%, demonstrating complete oral absorption of levofloxacin. Following a single intravenous dose of LEVAQUIN® 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. LEVAQUIN® Oral Solution and Tablet formulations are bioequivalent.

Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral or IV 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 concentrations 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 IV 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 dose of LEVAQUIN® with food prolongs the time to peak concentration by approximately 1 hour and decreases the peak concentration by approximately 14% following tablet and approximately 25% following oral solution administration. Therefore, LEVAQUIN® Tablets can be administered without regard to food. It is recommended that LEVAQUIN® Oral Solution be taken 1 hour before, or 2 hours after eating.

The plasma concentration profile of levofloxacin after IV administration is similar and comparable in extent of exposure (AUC) to that observed for LEVAQUIN® Tablets when equal doses (mg/mg) are administered. Therefore, the oral and IV routes of administration can be considered interchangeable (see Figure 2 and Figure 3).

Figure 2: Mean, Levofloxacin Plasma Concentration vs. Time Profile: 750 mg

Figure 3: Mean Levofloxacin Plasma Concentration vs. Time Profile: 500 mg

Distribution

The mean volume of distribution of levofloxacin generally ranges from 74 to 112 L after single and multiple 500 mg or 750 mg doses, indicating widespread distribution into body tissues. Levofloxacin reaches its peak levels in skin tissues and in blister fluid of healthy subjects at approximately 3 hours after dosing. The skin tissue biopsy to plasma AUC ratio is approximately 2 and the blister fluid to plasma AUC ratio is approximately 1 following multiple once-daily oral administration of 750 mg and 500 mg doses of LEVAQUIN®, respectively, to healthy subjects. Levofloxacin also penetrates well into lung tissues. Lung tissue concentrations were generally 2- to 5- fold higher than plasma concentrations and ranged from approximately 2.4 to 11.3 µg/g over a 24-hour period after a single 500 mg oral dose.

In vitro, over a clinically relevant range (1 to 10 µg/mL) of serum/plasma levofloxacin concentrations, levofloxacin is approximately 24 to 38% bound to serum proteins across all species studied, as determined by the equilibrium dialysis method. Levofloxacin is mainly bound to serum albumin in humans. Levofloxacin binding to serum proteins is independent of the drug concentration.

Metabolism

Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hours, whereas less than 4% of the dose was recovered in feces in 72 hours. Less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans. These metabolites have little relevant pharmacological activity.

Excretion

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