Levaquin - Clinical Pharmacology

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Renal insufficiency

Clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with impaired renal function (creatinine clearance <50 mL/ min), requiring dosage adjustment in such patients to avoid accumulation. Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or CAPD. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION.)

Hepatic insufficiency

Pharmacokinetic studies in hepatically impaired patients have not been conducted. Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

Bacterial infection

The pharmacokinetics of levofloxacin in patients with serious community-acquired bacterial infections are comparable to those observed in healthy subjects. Drug-drug interactions: The potential for pharmacokinetic drug inter-actions between levofloxacin and theophylline, warfarin, cyclosporine, digoxin, probenecid, cimetidine, sucralfate, and antacids has been evaluated. (See PRECAUTIONS: Drug Interactions.)

Table 1. Mean ±SD Levofloxacin PK Parameters Cmax Tmax AUC CL/ F 1 Vd/ F 2 t1/ 2 CLR

Regimen (µg/ mL) (h) (µg° h/ mL) (mL/ min) (L) (h) (mL/ min)

Single dose

250 mg p. o. 3 2.8 ± 0. 4 1.6 ± 1. 0 27.2 ± 3. 9 156 ± 20 ND 7.3 ± 0. 9 142 ± 21

500 mg p. o. 3 * 5.1 ± 0. 8 1.3 ± 0. 6 47.9 ± 6. 8 178 ± 28 ND 6.3 ± 0. 6 103 ± 30

500 mg i. v. 3 6.2 ± 1. 0 1.0 ± 0. 1 48.3 ± 5. 4 175 ± 20 90 ± 11 6.4 ± 0. 7 112 ± 25

750 mg p. o. 5 * 9.3 ± 1. 6 1.6 ± 0. 8 101 ± 20 129 ± 24 83 ± 17 7.5 ± 0. 9 ND

750 mg i. v. 5 11.5 ± 4. 0 4 ND 110 ± 40 126 ± 39 75 ± 13 7.5 ± 1. 6 ND

Multiple dose

500 mg q24h p. o. 3 5.7 ± 1.4 1.1 ± 0. 4 47.5 ± 6. 7 175 ± 25 102 ± 22 7.6 ± 1. 6 116 ± 31

500 mg q24h i. v. 3 6.4 ± 0. 8 ND 54.6 ± 11.1 158 ± 29 91 ± 12 7.0 ± 0. 8 99 ± 28

500 mg or 250 mg q24h i. v., 8.7 ± 4. 0 7 ND 72.5 ± 51.2 7 154 ± 72 111 ± 58 ND ND