PHARMACOKINETICS AND SAFETY OF LEVOFLOXACIN IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Levofloxacin, the bacteriologically active isomer of ofloxacin, has mi crobiologic activity against many pathogens common in human immunodefi ciency virus (HIV)-infected patients, including Mycoplasma species whi ch may be cofactors in the progression of HIV disease. The purpose of this phase I, double-blind, randomized (1:1), placebo-controlled trial was to evaluate the pharmacokinetics and safety of levofloxacin hemih ydrate in 10 asymptomatic HIV-infected males. Plasma concentrations by chiral high-performance liquid chromatography (HPLC) were evaluated f or 48 h after a single 350-mg oral dose, at morning predose during the multiple-dosing phase, and for 72 h at steady state after a week of 3 50 mg every 8 h orally. Mean +/- standard deviation levofloxacin pharm acokinetic parameters (by noncompartmental moment method) after multip le dosing were as follows: area under the concentration-time curve, 31 .24 +/- 5.60 mg . h/liter, apparent total body clearance, 11.18 +/- 1. 76 liters/h; renal clearance, 8.63 +/- 2.82 liters/h; steady-state vol ume of distribution, 104.10 +/- 12.48 liters; and effective half-life, 6.50 +/- 0.51 h. Single-dose parameters were not significantly differ ent from the multiple-dose parameters, with the exception of peak conc entrations in plasma, which were 4.79 +/- 1.00 and 6.92 +/- 1.56 mg/li ter for single- and multiple-dose data, respectively. Essentially iden tical parameter values were obtained from curve-fitting analysis when the entire 13-day plasma concentration profiles of the subjects were a nalyzed simultaneously by a two-compartmental distribution model. Levo floxacin pharmacokinetics in HIV-infected patients remained linear upo n multiple dosing. The dosing regimen studied provides levels in plasm a and urine well above those found to be effective in vitro against pa thogens common in HIV-infected patients. Levofloxacin was well-tolerat ed in this group of asymptomatic HIV-infected males; there were no sta tistically significant differences in adverse effects in the two group s (P = 0.22). Use of a placebo control helped to differentiate disease -related adverse effects from those related to the study drug.