PHARMACOKINETIC COMPARISON OF INTRAVENOUS AND ORAL CHLORAMPHENICOL IN PATIENTS WITH HEMOPHILUS-INFLUENZAE MENINGITIS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 67  (5) , 656-660
Abstract
The pharmacokinetics of chloramphenicol following i.v. and oral administration were studied in 14 infants with H. influenzae meningitis. Following 5 days of treatment with i.v. chloramphenicol (100 mg/kg per day every 6 h), oral chloramphenicol was substituted at the same dose. Multiple serum levels of chloramphenicol were determined after an i.v. dose on day 4 and after an oral dose on day 10. CSF levels were measured 6 h after i.v. or oral chloramphenicol dose on those days (CSF trough). Following i.v. administration, the mean peak serum level of 15.0 .mu.g/ml was reached at 45 min. In comparison, after oral chloramphenicol in the same dosage, the mean peak serum level of 18.5 .mu.g/ml was achieved at 2-3 h. The mean serum half-life of the drug (6.5 h) was significantly longer after oral administration than after i.v. chloramphenicol (4.0 h) (P < 0.001) The increased serum half-life following orally administered chloramphenicol was occasionally associated with drug accumulation. Mean trough CSF levels were somewhat higher when the patient received oral medication (6.6 .mu.g/ml) compared to i.v. administration (4.2 .mu.g/ml) (P < 0.001). For any treatment regimen for H. influenzae meningitis that includes a period of oral chloramphenicol therapy, the patient should be hospitalized to ensure compliance. Because of the wide range of individual variation in serum half-life that may result in accumulation, periodic monitoring of serum chloramphenicol levels is also recommended.