Probenecid Famotidine

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

H2 Receptor Antagonists (Famotidine/Ranitidine)/ Fexofenadine-Probenecid... 

Figure 8 Effect of probenecid on the plasma concentration of famotidine in healthy volunteers. Plasma concentration of famotidine was determined in healthy subjects treated with or without probenecid. The renal and tubular secretion clearances were decreased by the probenecid treatment (CLrenai 279 vs. 107 mL/min and CLsec 196 vs. 22 mL/min). Source (A) from Ref. 348 and (B) from Ref. 337.

OCT2 to the tubular secretion of cimetidine and famotidine. Furthermore, a great interspecies difference was found in the effect of probenecid, which had no effect on the tubular secretion of famotidine and cimetidine in rats (Fig. 8) (348). Two factors have been proposed for this interspecies difference (1) expression of Octl only in rodent kidney and (2) greater transport activity of famotidine by OAT3 than by Oat3 (120). In monkey, as in the case in human, probenecid had significant effect on the renal elimination of famotidine, but not for cimetidine (152). 

Inotsume N, Nishimura M, Nakano M, et al. The inhibitory effect of probenecid on renal excretion of famotidine in young, healthy volunteers. J Clin Pharmacol 1990 30 50-56. 

Diphenoxylate in high doses may produce dependence if coadministered with atropine. Diphenoxylate combined with thioridazine is associated with opioid withdrawal. Famotidine should be taken with care when coadministered with antacids, theophylline, and probenecid. Kaolin should not be administered with any other oral drug. Loperamide overdose should be treated with naloxone hydrochloride.174,175... 

Probenecid markedly decreases the renal clearance of famotidine and modestly reduces the renal clearance of cimetidine. However, these effects are not expected to result in adverse clinical effects. 

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