Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers.
The pharmacokinetics of cefprozil were determined with 12 volunteers (8 received cefprozil and 4 received a placebo) after oral administration of 500 mg every 12 h over an 8-day period in a randomized, double-blind, placebo-controlled design. Concentrations in serum and urine were measured by high-pressure liquid chromatography and bioassay. The pharmacokinetic parameters were calculated on the basis of an open one-compartment model. The mean maximum concentration in serum on day 1 was 11.5 +/- 2.6 mg/liter, and the time to reach maximum concentration was 122.3 +/- 30 min after administration. Bioavailability parameters (area under the concentration-time curve from zero to infinity, maximum concentration of the drug in serum, and urinary recovery) indicated an excellent absorption. No accumulation over the 8-day period was registered. Cefprozil had a short biological elimination half-life of 58 +/- 10 min and a renal clearance of 210 +/- 51 ml/min, indicating high rates of renal excretion and tubular secretion. Analysis of the fecal flora showed an ecological impact of cefprozil on the intestinal microflora, such as a moderate decrease in enterobacteria and a slight increase in enterococci, staphylococci, and bacteroides during the study. The number of all bacterial species was already normalized 4 days after the administration period. The tolerance of cefprozil proved to be excellent; only a slight and reversible increase of liver enzymes (in two volunteers), mild cephalalgia, tiredness, and soft stool were registered during the 8-day period. Cefprozil had excellent absorption, no accumulation over an 8-day period, and only a limited impact on the intestinal microflora.
Lode
H
H
Medical Department, Klinikum Steglitz, Freie Universität Berlin, Germany.
Müller
C
C
Borner
K
K
Nord
C E
CE
Koeppe
P
P
D000284:Administration, Oral; D000328:Adult; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007422:Intestines / Q000382:microbiology; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D000097670:Cefprozil
D002511:Cephalosporins; D000097670:Cefprozil