Dg. Therasse et al., EFFECTS OF RENAL DYSFUNCTION ON THE PHARMACOKINETICS OF LORACARBEF, Clinical pharmacology and therapeutics, 54(3), 1993, pp. 311-316
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.