We undertook a prospective study of the pharmacokinetics of penicillin G (administered intravenously every four hours for a total of b50,000 U per kilogram per day) in the cerebrospinal fluid of children with purulent meningitis. Both the absolute mean cerebrospinal-fluid penicillin concentration (0.8, 0.7 and 0.3 microgram per milliliter) and the percentage of the simultaneous serum penicillin concentration measurable in the cerebrospinal fluid (18.4, 9.9, 4.9 per cent) declined on the first, fifth and 10th days of therapy, respectively. A mean peak cerebrospinal-fluid penicillin concentration of 0.96 micrograms per milliliter was measured at least transiently on all three study days. This pharmacokinetic pattern correlated with the return of cerebrospinal-fluid protein concentration toward normal (P less than 0.01). Penicillin G in the dosage studied is adequate therapy for most streptococcal and meningococcal meningitis in children; an increased dosage may be necessary when the minimal inhibitory concentration of penicillin to the etiologic agent is unusually high.
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