Drug General Information (ID: DDIEWIJYKT)
Drug Name			Probenecid		Drug Info		Cefepime		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Uricosuric Agents				Antibiotics
Structure

Mechanism of Probenecid-Cefepime Interaction (Severity Level: Moderate)
Competitive inhibition of renal tubular secretion Click to Show/Hide Mechanism Graph
Drug Name		Probenecid				Cefepime
Mechanism		Competitive inhibition of renal tubular secretion of some cephalosporins				Cephalosporins
Key Mechanism Factor 1
		Factor Name		Renal tubular secretion
		Factor Description		Renal tubular secretion allows selective transfer of substances from the blood around the capillaries into the renal tubules via filtrate. Drug excretion may be reduced when two drugs compete for renal tubular secretion.
Mechanism Description		Decreased elimination of Cefepime caused by Probenecid mediated competitive inhibition of renal tubular secretion

Recommended Action
Management		Although probenecid has been used therapeutically to enhance serum levels of various beta-lactam antibiotics, the potential for increased adverse effects should be considered when probenecid is added to existing cephalosporin therapy, particularly when the latter is given at high dosages or to patients who are elderly or have renal dysfunction. Adjustment of the cephalosporin dosage may be required in accordance with the individual product labeling. For example, cefotaxime dosage should generally not exceed 6 grams/day when administered with probenecid. Probenecid reportedly does not affect the elimination of ceftazidime or ceftriaxone.

References
1	Brown G, Zemcov SJ, Clarke AM "Effect of probenecid on cefazolin serum concentrations." J Antimicrob Chemother 31 (1993): 1009-11. [PMID: 8360120]
2	Brown GR "Cephalosporin-probenecid drug interactions." Clin Pharmacokinet 24 (1993): 289-300. [PMID: 8491057]
3	Garton AM, Rennie RP, Gilpin J, Marrelli M, Shafran SD "Comparison of dose doubling with probenecid for sustaining serum cefuroxime levels." J Antimicrob Chemother 40 (1997): 903-6. [PMID: 9462447]
4	Griffith RS, Black HR, Brier GL, Wolny JD "Effect of probenecid on the blood levels and urinary excretion of cefamandole." Antimicrob Agents Chemother 11 (1977): 809-12. [PMID: 879735]
5	Ings RM, Reeves DS, White LO, et al "The human pharmacokinetics of cefotaxime and its metabolites and the role of renal tubular secretion on their elimination." J Pharmacokinet Biopharm 13 (1985): 121-42. [PMID: 4057054]
6	Kercsmar CM, Stern RC, Reed MD, et al "Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response." J Antimicrob Chemother 12 (1983): 289-95. [PMID: 6352634]
7	Ko H, Cathcart KS, Griffith DL, Peters GR, Adams WJ "Pharmacokinetics of intravenously administered cefmetazole and cefoxitin and effects of probenecid on cefmetazole elimination." Antimicrob Agents Chemother 33 (1989): 356-61. [PMID: 2729930]
8	DiPiro JT, Welage LS, Levine BA, et al. Single-dose cefmetazole versus multiple dose cefoxitin for prophylaxis in abdominal surgery.?J Antimicrob Chemother. 1989;23 Suppl D:71-77. [PMID: 2722725]
9	LeBel M, Paone RP, Lewis GP "Effect of probenecid on the pharmacokinetics of ceftizoxime." J Antimicrob Chemother 12 (1983): 147-55. [PMID: 6311785]
10	Luthy R, Blaser J, Bonetti A, Simmen H, Wise R, Siegenthaler W "Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime." Antimicrob Agents Chemother 20 (1981): 567-75. [PMID: 6275776]
11	Marino EL, Dominguez-Gil A "The pharmacokinetics of cefadroxil associated with probenecid." Int J Clin Pharmacol Ther Toxicol 19 (1981): 506-8. [PMID: 6795136]
12	LeBel M, Paone RP, Lewis GP. Effect of probenecid on the pharmacokinetics of ceftizoxime.?J Antimicrob Chemother. 1983;12(2):147-155. [PMID: 6311785]
13	Mischler TW, Sugerman AA, Willard DA, et al "Influence of probenecid and food on the bioavailability of cephradine in normal male subjects." J Clin Pharmacol 14 (1974): 604-11. [PMID: 4436447]
14	Nooyen SM, Overbeek BP, Delariviere AB, Storm AJ, Langemeyer JJ "Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting." Eur J Clin Microbiol Infect Dis 13 (1994): 1033-7. [PMID: 7889965]
15	Pitkin D, Dubb J, Actor P, et al "Kinetics and renal handling of cefonicid." Clin Pharmacol Ther 30 (1981): 587-93. [PMID: 7297018]
16	Product Information. Ceftin (cefuroxime). Glaxo Wellcome, Research Triangle Park, NC.
17	Product Information. Fortaz (ceftazidime). Glaxo Wellcome, Research Triangle Park, NC.
18	Product Information. Omnicef (cefdinir). Parke-Davis, Morris Plains, NJ.
19	Product Information. Rocephin (ceftriaxone). Roche Laboratories, Nutley, NJ.
20	Product Information. Tazicef (ceftazidime). SmithKline Beecham, Philadelphia, PA.
21	Product Information. Vantin (cefpodoxime proxetil). Pharmacia and Upjohn, Kalamazoo, MI.
22	Reeves DS, Bullock DW, Bywater MJ, Holt HA, White LO, Thornhill DP "The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers." Br J Clin Pharmacol 11 (1981): 353-9. [PMID: 7259928]
23	Santoro J, Agarwal BN, Martinelli R, et al "Pharmacology of cefaclor in normal volunteers and patients with renal failure." Antimicrob Agents Chemother 13 (1978): 951-4. [PMID: 677862]
24	Shukla UA, Pittman KA, Barbhaiya RH "Pharmacokinetic interactions of cefprozil with food, propantheline, metoclopramide, and probenecid in healthy volunteers." J Clin Pharmacol 32 (1992): 725-31. [PMID: 1487562]
25	Spina SP, Dillon EC "Effect of chronic probenecid therapy on cefazolin serum concentrations." Ann Pharmacother 37 (2003): 621-4. [PMID: 12708933]
26	Stoeckel K, Trueb V, Dubach UC, McNamara PJ "Effect of probenecid on the elimination and protein binding of ceftriaxone." Eur J Clin Pharmacol 34 (1988): 151-6. [PMID: 3383987]
27	Vlasses PH, Holbrook AM, Schrogie JJ, Rogers JD, Ferguson RK, Abrams WB "Effect of orally administered probenecid on the pharmacokinetics of cefoxitin." Antimicrob Agents Chemother 17 (1980): 847-55. [PMID: 7396472]
28	Welling PG, Dean S, Selen A, et al "Probenecid: an unexplained effect on cephalosporin pharmacology." Br J Clin Pharmacol 8 (1979): 491-5. [PMID: 508557]