Pharmacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis

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Abstract
Single-dose pharmacokinetics of ceftriaxone were determined in 19 patients with proven bacterial meningitis. The dosage was 50 mg of ceftriaxone per kg. The plasma concentration time curve declined in a biexponential manner. The mean peak plasma concentration was 207 micrograms/ml, and the elimination half-life was 4 h. In 12 patients, multiple-dose pharmacokinetics were determined after a loading dose of 75 mg of ceftriaxone per kg, followed by 50-mg/kg doses every 8 h in 5 patients or every 12 h in 7 patients. The mean peak plasma concentration was 230 micrograms/ml after the first dose and 263 micrograms/ml after the last dose. Of 12 patients, 5 had trough values that were larger after multiple doses than after a single dose. Mean penetration of ceftriaxone into cerebrospinal fluid was 3.1%. The median cerebrospinal fluid bactericidal titer against the patients pathogens was greater than 1:1,024 and less than 1:2,048. The drug was well tolerated without adverse effects.