Relationships between renal function and disposition of oral ciprofloxacin.
The relationships between creatinine clearance (CLCR) and the pharmacokinetics of oral ciprofloxacin were characterized. On the basis of these data, a dosage adjustment strategy, which incorporates the severity of infection and the size and renal function of the patient, was developed. An adaptive (feedback) control algorithm is proposed. A total of 32 subjects (8 normal, 8 anuric, and 16 with CLCR between 0.53 and 4.3 liters/h per 1.73 m2) were given a single 750-mg tablet of ciprofloxacin by mouth. Serial serum and urine samples were collected, assayed by high-pressure liquid chromatography, and comodeled. The population relationship between total apparent ciprofloxacin clearance (CL/f) and CLCR, both measured in liters per hour per 1.73 m2, was CL/f = 2.83 x CLCR + 21.8 (r = 0.69; P less than 0.001). The mean terminal half-life was not significantly related to CLCR but was much more variable in subjects with CLCR less than 3 liters/h per 1.73 m2 (F = 4.8; P less than 0.005). We conclude that patients with CLCR less than 1.2 liters/h per 1.73 m2 should receive two-thirds of the normal daily dose and that the dose interval should not be lengthened.
Forrest
A
A
School of Pharmacy, University of Maryland, Baltimore 21201.
Weir
M
M
Plaisance
K I
KI
Drusano
G L
GL
Leslie
J
J
Standiford
H C
HC
D000284:Administration, Oral; D000328:Adult; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D002939:Ciprofloxacin; D003404:Creatinine