Multiple-dose pharmacokinetics of sparfloxacin and its influence on fecal flora.
In a randomized, double-blind, placebo-controlled, multiple-dose pharmacokinetic study, the safety and effect on intestinal flora of sparfloxacin (SPX) were determined in 12 healthy male volunteers (8 received SPX and 4 received a placebo). Following fasting and oral administration of 400 mg on day 1 and 200 mg on days 2 to 8, concentrations of the free drug in serum, urine, and feces were measured by high-performance liquid chromatography; serum and urine were also evaluated by a microbiological assay. All results, except those for renal excretion, exclude the glucuroconjugate metabolite. A mean peak concentration in serum (400-mg dose) of 0.56 +/- 0.13 mg/liter was measured 3.52 +/- 0.98 h after administration. Pharmacokinetic parameters (measured by high-performance liquid chromatography) were based on an open, one-compartment model and resulted in the following day 1 (calculated for the 200-mg dose), day 4 (recalculated for a single dose), and day 8 values (mean +/- standard deviation): area under the curve, 16.4 +/- 2.3 (day 1) and 18.3 +/- 5.1 (day 4) mg.h/liter; elimination half-life, 18.3 +/- 3.9 h; steady-state volume of distribution, 4.7 +/- 1.4 (day 1) and 4.3 +/- 1.2 (day 8) liters/kg; apparent total clearance, 201 +/- 31 (day 1) and 190 +/- 51 (day 4) ml/min; renal clearance, 19.1 +/- 5.8 (day 1) and 23.2 +/- 19.4 (day 4) ml/min. Recovery in urine on day 1 was 5.89% +/- 1.4% of the dose in 24 h for the parent compound and 18.4% +/- 6.8% for the SPX glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)
Ritz
M
M
Department of Pulmonary and Infectious Diseases, City Hospital Berlin-Zehlendorf, Germany.
Lode
H
H
Fassbender
M
M
Borner
K
K
Koeppe
P
P
Nord
C E
CE
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001681:Biological Assay; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology*; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008954:Models, Biological; D011485:Protein Binding; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D001798:Blood Proteins; D024841:Fluoroquinolones; D015363:Quinolones; C061363:sparfloxacin