Disposition of cefpodoxime proxetil in hemodialysis patients.
The disposition of cefpodoxime after single, oral 200-mg doses of cefpodoxime proxetil (cefpodoxime equivalents) was investigated in an open-label study of six patients with end-stage renal disease currently maintained on hemodialysis. Subjects were randomly assigned to one of two treatment groups, which differed in the sequence of the interdialytic and intradialytic periods. Doses were separated by at least 2 weeks. Blood samples were serially collected for 48 hours after each treatment; if obtainable, urine was also collected over this same period. During the intradialytic period, hemodialysis was scheduled to begin approximately 3 hours after dosing, and dialysate was collected before and until the end of dialysis. Average cefpodoxime elimination half-life for the interdialytic period was 18.0 +/- 6.5 hours; apparent total body clearance was 28.6 +/- 13 mL/minute. The half-life during hemodialysis, 2.66 +/- 0.74 hours, was considerably shorter than that after hemodialysis, 19.2 +/- 3.5 hours, in the intradialytic period of the study. Hemodialysis clearance of cefpodoxime was 120 +/- 31 mL/minute, which was 57.1 +/- 13% and 71.7 +/- 25% of the hemodialysis clearance for urea nitrogen and creatinine, respectively. The 2.86 +/- 0.25 hour hemodialysis session removed 22.4 +/- 2.9% of the administered dose, as assessed by cefpodoxime recovery in dialysate. A maximum rebound in cefpodoxime plasma concentration of 0.41 +/- 0.33 mcg/mL was observed, at about one-half hour after the end of hemodialysis. Based on these results, dosage adjustment is not required, but extension of the dosing interval is warranted.(ABSTRACT TRUNCATED AT 250 WORDS)
Borin
M T
MT
Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49007.
Hughes
G S
GS
Kelloway
J S
JS
Shapiro
B E
BE
Halstenson
C E
CE
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015296:Ceftizoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D000097627:Cefpodoxime Proxetil
D015296:Ceftizoxime; D011355:Prodrugs; D000097627:Cefpodoxime Proxetil