cefzil and Liver-Diseases

Cefprozil is a new orally administered cephalosporin with a spectrum of in vitro activity similar to that of cefuroxime. The pharmacokinetics of cefprozil are linear relative to dose size. Gastrointestinal absorption produces maximal plasma concentrations of approximately 10 mg/L 1-2 hours after administration of an oral dose of 500 mg. Approximately 94% of the dose is absorbed, and 60%-70% is excreted in the urine as unchanged drug. The renal clearance exceeds the glomerular filtration rate, thus suggesting active tubular secretion. Administration with food or antacids produces negligible effects on the rate or extent of absorption. Kinetic disposition in the elderly is similar to that in young healthy individuals, but elimination is slightly slower in infants and children. Because renal impairment, but not hepatic dysfunction, significantly reduces the elimination of cefprozil, it is recommended that the dosage be reduced by 50% in patients whose creatinine clearance is less than 30 mL/min. Penetration of the interstitial fluid by cefprozil is excellent, with concentrations approaching those observed in the plasma. The pharmacokinetic disposition of cefprozil, coupled with its in vitro activity, supports the use of once- or twice-daily dosage regimens.

Topics: Age Factors; Aged; Animals; Bacteria; Biological Availability; Cefprozil; Cephalosporins; Female; Food; Humans; Intestinal Absorption; Kidney Diseases; Liver Diseases; Male; Tissue Distribution

The pharmacokinetics of cefprozil were studied in 12 (9 men, 3 women) subjects with hepatic impairment and in 12 healthy subjects who were matched for age, sex, and weight. Each subject received a single 1000 mg oral dose of cefprozil, which consists of cis and trans isomers in approximately a 90:10 ratio. Serial blood and urine samples were collected and analyzed using validated HPLC/UV methods for the concentration of each isomer. The results of the plasma and urine analyses were subjected to noncompartmental pharmacokinetic analysis. The values for the peak plasma concentrations (Cmax), area under the plasma concentration versus time curve (AUC0-infinity), apparent total body clearance (Clt/F), renal clearance (Clr), and percent of drug excreted in urine (%UR) of each isomer were not significantly different in healthy subjects and patients with hepatic impairment. The only parameters that were significantly (P less than or equal to .05) longer in patients with hepatic impairment were mean residence time in the body (MRT) and half-life; the MRT for the cis isomer in healthy subjects and subjects with hepatic impairment were 3.33 hr and 3.88 hr, respectively, and for the trans isomer 3.17 hr and 3.68 hr; the half-life for the cis isomer was 1.62 hr and 2.22 hr, respectively, and for the trans isomer 1.21 hr and 1.54 hr. The pharmacokinetics of the cis and trans isomers of cefprozil were virtually identical in healthy subjects as well as those with hepatic impairment.

Topics: Administration, Oral; Adolescent; Adult; Cefprozil; Cephalosporins; Female; Humans; Isomerism; Liver Diseases; Male; Metabolic Clearance Rate; Middle Aged