Effect of Chronic Probenecid Therapy on Cefazolin Serum Concentrations

• Published in: The Annals of pharmacotherapy 2003-05, Vol.37 (5), p.621-624
• Main Authors: Spina, Sean P, Dillon, Edward C, Jr
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Biological and medical sciences; Cefazolin - administration & dosage; Cefazolin - adverse effects; Cefazolin - blood; Cefazolin - pharmacokinetics; Drug Interactions; Female; Humans; Injections, Intravenous; Male; Medical sciences; Middle Aged; Probenecid - administration & dosage; Probenecid - adverse effects; Probenecid - pharmacology
• ISSN: 1060-0280; 1542-6270
• DOI: 10.1345/aph.1C347

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.