Pharmacokinetics of cefprozil in healthy subjects and patients with renal impairment.
Cefprozil, a new broad-spectrum oral cephalosporin, is composed of cis and trans isomers in an approximate 90:10 ratio. The pharmacokinetics of a single oral 1000-mg dose of cefprozil were evaluated in 6 healthy subjects and 24 patients with various degrees of renal impairment. Six of these subjects were studied both while receiving hemodialysis and during an interdialytic period. Plasma, urine, and hemodialysate that were collected at predetermined times were analyzed for concentrations of the cis and trans isomers of cefprozil using reverse-phase HPLC assay with UV detection. The maximum plasma concentration of the cis isomer ranged from 12.3 micrograms/mL in subjects with normal renal function to 36.7 micrograms/mL in hemodialysis patients. Similarly the area under the plasma concentration-time curve and the elimination half-life increased from 46 micrograms.h/mL to 373 micrograms.h/mL and from 1.72 hours to 5.94 hours, respectively. Renal clearance of the cis isomer decreased from 198 mL/min in normal subjects to 19 mL/min in volunteers with creatinine clearances of less than or equal to 30 mL/min; there was a strong correlation (r2 greater than or equal to .93) between the renal clearance of the cis isomer and creatinine clearance. Urinary recovery of the cis isomer decreased from 57% in those with normal renal function to 24% in the group with a creatinine clearance of less than or equal to 30 mL/min. Hemodialysis decreased the half-life of the cis isomer to 2 hours and removed approximately 55% of it from the body during a 3-hour dialysis period (hemodialysis clearance equaled approximately 87 mL/min). The pharmacokinetics of the trans isomer were similar to those observed for the cis isomer and were affected similarly by declining renal function. A reduction in dosage is recommended in patients with a creatinine clearance of 30 mL/min or less. It may be necessary to administer a dose after hemodialysis to maintain therapeutic plasma concentrations.
Shyu
W C
WC
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute Syracuse, New York 13221-4755.
Pittman
K A
KA
Wilber
R B
RB
Matzke
G R
GR
Barbhaiya
R H
RH
D000284:Administration, Oral; D000328:Adult; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007536:Isomerism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis; D000097670:Cefprozil
D002511:Cephalosporins; D000097670:Cefprozil