Pharmacokinetics of ertapenem in patients with varying degrees of renal insufficiency and in patients on hemodialysis.
Ertapenem is a parenteral beta-lactam carbapenem antibiotic. This open-label study examined the pharmacokinetics of single 1-g intravenous doses of ertapenem, administered over 30 minutes, in patients with mild, moderate, and advanced renal insufficiency (RI) and in patients with end-stage renal disease (ESRD) requiring hemodialysis. Pharmacokinetics were compared with historical controls pooled across healthy young and elderly subjects. Area under the concentration-time curve from time zero to infinity increased 7% in mild, 53% in moderate, 158% in advanced RI, and 192% in ESRD; end of infusion concentration changed minimally; half-life was 4.5 hours in the historical control group and 4.4, 6.1, 10.6, and 14.1 hours in mild RI, moderate RI, advanced RI, and ESRD, respectively. Hemodialysis cleared approximately 30% of the dose. The recommended dose in mild to moderate RI and after hemodialysis is unchanged at 1 g daily; and in advanced RI and ESRD is reduced to 0.5 g daily. If the daily dose is given 6 hours prior to hemodialysis, a supplementary 150-mg dose (30% of the daily dose) is recommended postdialysis.
Mistry
Goutam C
GC
Department of Clinical Pharmacology, Merck Research Laboratories, Rahway, New Jersey 07065, USA. goutam_mistry@merck.com
Majumdar
Anup K
AK
Swan
Suzanne
S
Sica
Domenic
D
Fisher
Alison
A
Xu
Yang
Y
Hesney
Michael
M
Xi
Liwen
L
Wagner
John A
JA
Deutsch
Paul J
PJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D004334:Drug Administration Schedule; D000077727:Ertapenem; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000378:metabolism / Q000628:therapy*; D013997:Time Factors; D047090:beta-Lactams / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077727:Ertapenem