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Interaction of chloramphenicol with phenytoin and phenobarbital; Case report
Author(s) -
Koup Jeffrey R.,
Gibaldi Milo,
McNamara Patrick,
Hilligoss Donald M.,
Colburn Wayne A.,
Bruck Erika
Publication year - 1978
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1978245571
Subject(s) - phenytoin , phenobarbital , chloramphenicol , pharmacology , medicine , chemistry , epilepsy , antibiotics , psychiatry , biochemistry
The effect of chloramphenicol therapy (48 mg/kg/day) on the serum concentrations of phenytoin and phenobarbital was studied in a patient previously stabilized on anticonvulsant medications. Phenytoin, 12 mg/kg/day, and phenobarbital, 5 mg/kg/day resulted in serum concentrations averaging 10.8 µ/ml before and 30.5 µ/ml, after chloramphenicol therapy. A reduction in dose of both phenytoin and phenobarbital was required to minimize adverse effects during the course of chloramphenicol therapy. An average daily dose of phenytoin of 9.1 mg/kg resulted in an average serum concentration of 17.8 µ/ml. A daily dose of phenobarbital of 4.0 mg/kg resulted in an average serum concentration of 37.1 µ/ml. These changes indicate 50.5% and 40.4% decreases in clearance of phenytoin and phenobarbital. Multiple‐dose nonlinear regression analysis of phenytoin and phenobarbital serum concentration data obtained during chloramphenicol therapy indicated a 62.5% and a 29.5% decrease in clearance. Subsequent serum concentration monitoring demonstrated a similar reduction in phenobarbital clearance when chloramphenicol was added to phenobarbital alone.