Cefazolin 2 Grams IV with Probenecid 1 Gram Every 24 Hours
Yes, cefazolin 2 grams IV can be safely administered with probenecid 1 gram once daily in adults with normal renal function, as probenecid effectively prolongs cefazolin serum concentrations by blocking its tubular secretion, allowing for less frequent dosing while maintaining therapeutic levels. 1
Pharmacokinetic Rationale
Probenecid blocks the renal tubular secretion of cefazolin, which is the primary route of elimination for this cephalosporin, thereby increasing the area under the concentration-time curve and prolonging the serum half-life 2
In normal subjects, cefazolin has a serum half-life of approximately 1.6-2.2 hours, which is prolonged by 20-40% when probenecid is administered concomitantly 2, 3
The renal clearance of cefazolin is reduced when probenecid is given, with more than 90% of the cefazolin dose normally recovered in urine within 24 hours in patients with normal renal function 2
Evidence for Once-Daily Dosing with Probenecid
A prospective study demonstrated that probenecid 500 mg orally four times daily effectively maintained therapeutic serum concentrations of cefazolin at steady-state when given with intravenous cefazolin 2000 mg once daily 1
In this study, patients receiving cefazolin 2000 mg once daily with probenecid achieved average peak concentrations of 146.53 mg/L on day 1 and 148.30 mg/L on day 5, with trough concentrations of 2.02 mg/L and 2.67 mg/L, respectively 1
These trough levels remained therapeutic throughout the dosing interval, confirming that probenecid successfully extends the duration of adequate cefazolin concentrations 1
Practical Dosing Algorithm
Administer cefazolin 2 grams IV once every 24 hours as an infusion over 30-60 minutes 1
Give probenecid 1 gram orally at the time of cefazolin administration (note: the cited study used 500 mg four times daily for a total of 2 grams daily, but 1 gram once daily may provide adequate inhibition based on the pharmacokinetic data showing probenecid's EC50 for inhibiting tubular secretion is 0.80 mg/L) 4
For optimal effect, probenecid can be given 1 hour before cefazolin administration, as pretreatment produces a greater increase in cefazolin AUC compared to concomitant administration 5
Important Caveats and Monitoring
This regimen is appropriate only for patients with normal renal function; dose adjustments are required for renal impairment, as the elimination rate constant correlates linearly with creatinine clearance 2, 3
In patients with severe renal impairment, the serum half-life of cefazolin extends dramatically (up to 42 hours in anephric patients), and probenecid should be avoided or used with extreme caution 2
The dose-response relationship for probenecid shows that higher doses (2 grams) produce greater increases in cefazolin AUC than lower doses (1 gram), so if using only 1 gram daily rather than divided doses, monitor clinical response closely 5
Probenecid at therapeutic doses will block tubular excretion of cefazolin almost completely, but this effect is concentration-dependent 4
Clinical Context from Guidelines
While the specific combination of cefazolin 2 grams with probenecid 1 gram daily is not explicitly detailed in major guidelines, cefazolin is recommended at doses up to 100 mg/kg/day divided every 8 hours (maximum 12 grams daily) for serious infections such as endocarditis 6
For intra-abdominal infections, cefazolin 1-2 grams every 8 hours is listed as an acceptable regimen in adults with normal renal function 6
The use of probenecid to extend dosing intervals represents a practical strategy to reduce administration frequency while maintaining efficacy, particularly useful for outpatient parenteral antibiotic therapy 1
Potential Pitfalls to Avoid
Do not use this regimen in patients with renal impairment without adjusting the cefazolin dose and potentially avoiding probenecid altogether, as drug accumulation can occur 2, 3
Avoid assuming that 1 gram of probenecid once daily will produce identical effects to 500 mg four times daily; the latter has been specifically studied and validated 1
Monitor for probenecid-related adverse effects including gastrointestinal upset, rash, and potential drug interactions with other renally cleared medications 5
Ensure adequate hydration, as probenecid can increase the risk of uric acid crystalluria in some patients 5