Case 2 Phenobarbital-Chloramphenicol drug interaction    Signalment:  3.5 year old male German Shepherd Chief Complaint:  Acute onset of depression, anorexia and lethargy. Pertinent History:  Diagnosed as epileptic 1 year prior to presentation. Patient was suffering from severe cluster seizures. Response to phenobarbital was initially acceptable but seizures worsened and potassium bromide added to regimen 3 weeks prior to presentation. Response to combination therapy acceptable. Patient presented for cough one week prior to presentation. Lower respiratory infection diagnosed and antibiotic therapy begun. Three days later, patient presented for chief complaint. Vital signs on physical examination are normal. Clinical laboratory tests are normal. Phenobarbital one week prior to presentation was 32 mg/ml (not certain if a peak or trough sample). Drug of Interest:  Bromide Concern:  Toxicity Other Drugs:  Phenobarbital 4 mg/kg every 12 hours orally (at current dose for 2 weeks; last phenobarbital collected was at steady-state using current dosing regimen); chloramphenicol 25 mg/kg every 8 hours for 3 days. Dosing Regimen:  A 450 mg/kg loading dose measured 6 months prior to presentation was 0.9 mg/ml. The maintenance dose was 10 mg/kg every 12 hours. The maintenance dose was increased to 15 mg/kg but concentrations were not subsequently re-measured at steady state. Duration of Current Regimen:  Bromide, 6 months. Phenobarbital: 1 year. Chloramphenicol: 4 days. Patient Response:  Seizure control improved, patient not groggy until recent episode. Drug Concentration:  Bromide: 2.10 mg/ml Time:  12 hours Drug Elimination Half-Life:  NA Volume of Distribution:  NA Predicted Peak:  NA Predicted Trough:  NA Recommendation:  Bromide concentrations are not sufficiently increased to cause clinical signs. Phenobarbital concentrations were measured: peak concentrations were 50 mg/ml; trough concentrations were 46 mg/ml. Phenobarbital elimination half-life was 58 hours. Comments:  This patient was presented for presumed bromide toxicity. However, the bromide concentrations were not consistent with the profound depression the patient was exhibiting. Phenobarbital concentrations were checked to identify possible contribution to lethargy using a sample of blood collected just prior to the onset of chloramphenicol therapy. Phenobarbital concentrations had indeed increased in this patient by 40% - 50% despite no dose change. The increase was presumed to be due to chloramphenicol therapy. Chloramphenicol is a potent inhibitor of drug metabolizing enzymes, resulting in decreased phenobarbital clearance. Drug elimination half-life had not been previously determined for phenobarbital in this patient so a change in half-life could not be documented. Follow-Up:  Chloramphenicol therapy was decreased. Phenobarbital therapy was discontinued for one drug elimination half-life and restarted at the same dose. Within 48 hours, patient was normal. [back to top]