The Pharmacokinetics and Serum and Urine Bactericidal Activity of Ciprofloxacin

Ciprofloxacin is an investigational quinolone agent possessing an impressive antibacterial spectrum. Its pharmacokinetics were studied in six volunteers after 250‐mg and 500‐mg single oral doses, and its bactericidal activity compared to that of trimethoprim‐sulfamethoxazole given to the same volunteers. Mean peak serum levels were 1.45 μg/mL and 2.46 μg/mL for 250‐mg and 500‐mg doses, and time to peak was 1 and 1.3 hours. The 12‐hour levels were 0.12 μg and 0.22 μg. Half‐life (T1/2)α were 0.32 and 0.43 with T1/2β were 3.97 and 4.15 and volume of distribution (area) were 80L and 90L, respectively. Area under the concentration curve (AUC) was 5.65 h · μg/mL and 10.37h · μg/mL. Serum clearance was 23L for both doses. Approximately 49% of the 250‐mg dose and 43% of the 500‐mg dose was recovered in the urine. Bactericidal levels were determined against clinical isolates. Sera at 1.5 hours after the 500‐mg dose averaged bactericidal levels of 1:20 or better for an Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,and beta‐lactamase producing Haemophilus influenzae and Branhamella catarrhalis. Urinary bactericidal levels at eight to 12 hours were 1:157 for E coli, K pneumoniae, gentamicin‐piperacillin resistant P aeruginosa, Staphylococcus aureus, and 1:20 for Streptococcus faecalis. Serum bactericidal levels were superior, and urine bactericidal levels were superior or equal to the bactericidal levels obtained with trimethoprim‐sulfamethoxazole. Ciprofloxacin's in vitro activity and human pharmacology should permit a twice or once daily dosing schedule for system 1C infections due to most Enterobacteriaceae, Haemophilus, Branhamella and Pseudomonas, and S aureus, and once daily for urinary gastrointestinal infections.