Renal handling of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, in rabbits in comparison with meropenem

Xenobiotica. 2006 Dec;36(12):1273-87. doi: 10.1080/00498250600944326.

Abstract

The plasma half-life of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, is longer than that of meropenem in animals and humans. To address this issue, renal clearance studies were conducted in rabbits. A constant rate infusion of CS-023 and meropenem was conducted in male Japanese White rabbits. Concentrations in the plasma, urine and renal cortex were measured to evaluate renal clearance and renal tissue uptake. CS-023 showed a clearance ratio (renal clearance/glomerular filtration rate) of around 1, which was not affected by co-administration of probenecid or p-aminohippurate. On the other hand, meropenem exhibited a clearance ratio of around 3, which was significantly decreased to 1 by co-administration of probenecid. p-Aminohippurate, in contrast, had no effect. The renal cortex/plasma concentration ratio of CS-023 was around 0.6 with or without probenecid co-administration. This ratio of meropenem was around 3, which was decreased significantly by co-administration of probenecid to around 0.6. These data suggest that meropenem is secreted in the renal tubules via organic anion transporters, but CS-023 is not. The present findings in rabbits would indicate that a lack of renal tubular secretion of CS-023 is a reason for the long plasma half-life compared with meropenem.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Carbapenems / pharmacokinetics*
  • In Vitro Techniques
  • Kidney / metabolism*
  • Kidney Cortex / metabolism
  • Kidney Tubules / metabolism
  • Male
  • Meropenem
  • Metabolic Clearance Rate
  • Microsomes / metabolism
  • Models, Animal
  • Rabbits
  • Thienamycins / pharmacokinetics*

Substances

  • Carbapenems
  • Thienamycins
  • tomopenem
  • Meropenem