Effect of chronic probenecid therapy on cefazolin serum concentrations.
OBJECTIVE
To prospectively assess the effectiveness of probenecid at maintaining therapeutic serum concentrations of cefazolin at steady-state by comparing cefazolin serum concentrations produced by intravenous cefazolin 2000 mg every 8 hours with concentrations produced by once-daily administration of intravenous cefazolin 2000 mg plus oral probenecid 500 mg 4 times daily.


METHODS
Patients in this prospective, nonrandomized, unblinded study were identified after an order was written for intravenous cefazolin 2000 mg every 8 hours or once daily plus oral probenecid 500 mg 4 times daily in the emergency department. For both study arms, a peak cefazolin serum concentration was obtained 1 hour after the infusion was started and 23 hours later, prior to the next scheduled dose. Doses of cefazolin for days 2-4 were then administered as ordered. On day 5, peak and trough serum concentrations were drawn 1 hour after the infusion started and 23 hours later, respectively.


RESULTS
A total of 26 patients were prospectively assessed from April 2000 to October 2001. In patients who received cefazolin once daily, the average serum peak and trough concentrations on day 1 were 146.53 and 2.02 mg/L, respectively. Peak and trough concentrations on day 5 were 148.30 and 2.67 mg/L, respectively. In patients who received cefazolin every 8 hours, peak and trough concentrations were 122.15 and 18.65 mg/L on day 1 and, on day 5, 136.51 and 16.98 mg/L, respectively.


CONCLUSIONS
Probenecid 500 mg given orally 4 times daily was effective in maintaining therapeutic serum concentrations of cefazolin at steady-state when given with intravenous cefazolin 2000 mg once daily.
Spina
Sean P
SP
Pharmacy Department, Royal Columbian Hospital, New Westminster, British Columbia, Canada. sean.spina@fraserhealth.ca
Dillon
Edward C
EC
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002437:Cefazolin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011339:Probenecid / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*
D002437:Cefazolin; D011339:Probenecid