Pharmacokinetics and safety of single oral doses of lomefloxacin.

The pharmacokinetics of 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg of lomefloxacin, a quinolone antimicrobial, were examined in a single sequential rising dose, placebo-controlled, crossover study. Each of 30 healthy male subjects (6 per group) received placebo and one dose of lomefloxacin, separated by 5 days. Test results (physical examinations, laboratory and hematology panels, vital signs, neurological and ophthalmological examinations, EEG or urinalysis) revealed no clinically significant differences compared to baseline. Mean Cmax values (0.92 micrograms ml-1 to 6.99 micrograms ml-1) increased linearly with dose. Mean tmax averaged 1.13 +/- 0.5 h and mean t1/2, 7.8 +/- 1.0 h over all doses. There was a small influence of dose on the AUC0-48. Mean urinary concentrations during the first 4 h postdosing ranged from 79 to 454 micrograms ml-1. Urine concentrations remained greater than or equal to 15 micrograms ml-1 over 24 h at the lowest dose. Maximum urinary excretion rate, Rmax, ranged from 5.84 mg h-1 to 34.90 mg h-1. Dose normalized Rmax and XU96 (per cent of dose) were unaffected by dose. Mean renal clearance decreased at higher doses. In conclusion, lomefloxacin was well tolerated in doses up to 800 mg. Lomefloxacin is rapidly absorbed with an elimination half-life of approximately 8 h. The data suggest that the drug can be effectively administered once daily.

Microbioluminometry assay: determination of erythromycin activity in plasma or serum.

A microbioluminometry assay (MBA) was developed for the quantitative analysis of erythromycin activity in human plasma or serum. The MBA method is adapted from turbidimetric methods and utilizes an enzyme-catalyzed bioluminescence reaction to quantitate the growth of Staphylococcus aureus in liquid culture medium. Statistical analysis of data obtained in method validation studies and in more than 500 assays of standard curve and control samples demonstrates consistent reproducibility and accuracy within theoretical limits. The MBA was shown to be more sensitive than agar diffusion assays with a lower limit of sensitivity less than 20.0 ng/mL and coefficients of variation less than 10%. Cumulative results of 178 assays of spiked control plasma samples in the range of 0.14-2.18 micrograms/mL show 11.2% of individual determinations are greater than +/- 15% the expected value, and 5.6% of individual determinations are greater than +/- 20% the expected value. Bioavailability profiles obtained with MBA are consistent with reported data for erythromycin. Values for 206 subject samples analyzed by MBA and agar diffusion assays showed a high degree of correlation (r = 0.9525) between the two methods. The MBA technique provided high sample throughput because of the use of microtiter plate technologies; it is also economical since it requires less sample and reagents.