The influence of trimethoprim, sulfamethoxazole, and creatinine on renal organic anion and cation transport in rat kidney tissue

Sulfamethoxazole-induced crystal nephropathy: characterization and prognosis in a case series

“…A study by Berglund et al in 1975 showed that TMP caused a significant increase in plasma creatinine levels without affecting GFR 10 . Lee observed a similar effect studying the influence of TMP on tubular transport of organic anions and cations in rat kidney tissue 11 . Shouval noted that CMX caused transient changes in plasma creatinine and creatinine clearance 8 .…”

“…Due to a higher incidence of toxicity in patients with acute kidney injury or pre-existing chronic kidney disease, dosage adjustment of CMX and close therapeutic monitoring are required, especially for patients with impaired glomerular filtration rate (GFR) 6 , 7 . A functional effect of Trimethoprim (TMP) on tubular creatinine secretion has been extensively characterized, which may artificially increase serum creatinine levels, even in the absence of acute kidney injury 8 – 11 .…”

Trimethoprim, Creatinine and Creatinine-Based Equations

“…Trimethoprim is a cationic drug and its effect on tubular creatinine secretion is similar to that of cimetidine [37]. Both act as inhibitors of organic cation transport via which creatinine is secreted in the distal tubule [28,38,39,40]. This has been well documented in both cell cultures and animal studies [38].…”

Pharmacokinetic Interaction between Zidovudine and Trimethoprim/sulphamethoxazole in HIV‐1 Infected Children

“…It was our hypothesis that an interaction between TMP/SMX and ZDV could occur at the level of renal tubular secretion through competition for similar renal membrane transporters. In contrast with adult patients, we expected that this interaction would likely result in a clinically significant alteration in ZDV Cl o in young children due to the immaturity of the metabolic pathways (13). As a result, Cl r pathways of drugs that are highly metabolized by the liver become an increasingly impor- tant route for overall drug elimination in young children, further contributing to the possibility of renal drug-drug interactions.…”

“…This type of crossreactivity with respect to both organic anion and organic cation transporters in the kidney has been demonstrated with other zwitterionic compounds including the cephalosporins, cephaloridine and cefadroxil (10,11). TMP is an organic cation known to undergo renal tubular secretion through the organic cation system (12), whereas SMX, an organic anion, is eliminated via the organic anion system (13). Therefore, ZDV and TMP/SMX may interact at the level of the kidney through competition for similar renal tubular transport systems.…”