EFFECTS OF RENAL DYSFUNCTION ON THE PHARMACOKINETICS OF LORACARBEF

Loracarbef, the first carbacephem antibiotic to undergo clinical devel opment, is excreted primarily unchanged in the urine (>90%). Data anal yzed from subjects with various degrees of renal dysfunction who were given single oral doses of loracarbef indicated a linear relationship between creatinine clearance (CL(CR)) and plasma clearance [CL(P) (L/h r) = 0.106 . CL(CR) (ml/min/1.73 m2)]. The mean area under the plasma concentration-time curve in normal subjects and in patients with sever e renal insufficiency (no dialysis/receiving dialysis) was 32 mug . hr /ml and 1085 mug . hr/ml/103 mug . hr/ml, respectively. Therefore, for individuals with moderate renal insufficiency (CL(CR), 10 to 49 ml/mi n/1.73 m2), the dose should be halved or the dosing interval doubled; patients with severe renal insufficiency who are not receiving dialysi s should be treated with the normal dose given once every 3 to 5 days. Loracarbef is readily cleared from plasma by hemodialysis; dosing sho uld be repeated after a hemodialysis treatment.