Cimetidine organic cation transport

The rate and extent of intestinal absorption of cimetidine has been widely discussed previously, and a reasonable value of fa for this drug has been estimated as 75% [90, 91]. It has been reported that cimetidine is a substrate for both P-gp and/ or organic cation transporters (OCNT1 and OCNT2) [82, 92]. We determined the... 

PROCAINAMIDE H2 RECEPTOR BLOCKERS Cimetidine may t plasma concentrations of procainamide Cimetidine is a potent inhibitor of organic cation transport in the kidney, and elimination of procainamide is impaired. Cimetidine also inhibits CYP2D6-mediated metabolism of procainamide. Ranitidine is a much weaker CYP2D6 inhibitor Monitor PR and BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider alternative acid-suppression therapy... 

The nephrotoxicity of dsplatin is reduced in humans [132], mice [133] and dogs [134] by co-admin-istration of probenecid, suggesting that cisplatin is transported by the PAH transport system. It has been proposed that platinum, hke other nephrotoxic metal ions such as mercury and potassium dichromate, are taken up by tubular cells as sulphydryl conjugate through a probenecid-sensitive pathway [133]. However, cisplatin might also be transported by the organic cation transport system, since quinidine, cimetidine and ranitidine inhibited its net secretion flux in the dog kidney [134]. 

The OAT family of transporters can be inhibited by probenecid. If a substrate of this family of transporters, such as penicillin, is administered concomitantly with probenecid, the dmg can have decreased renal secretion, with a resulting increase in the plasma penicillin concentration. Cimetidine is an inhibitor of members of the OAT, organic cation transporter (OCT) and OATP families of transporters This inhibition has been shown to result in a decrease in the renal excretion of substrates such as procainamide and levofloxacin, resulting in increased plasma concentrations of these dmgs. 

Cimetidine is a non-specific cytochrome P450 isoenzyme inhibitor, but it would seem that in most cases, with the exception of loratadine, these enzyme inhibitory effects do not significantly affect the metabolism of antihistamines. More recent evidence has shown cimetidine can also affect drug transporter proteins, in particular it may inhibit organic cation transporters. However, it probably does not affect anion transporter proteins since it does not affect the plasma pharmacokinetics of fexofenadine, which is a substrate of these transporters. ... 

Lamivudine is cleared predominantly from the body by the kidneys using the organic cationic transport system however, cimetidine and ranitidine, which partly use this mechanism, do not interact with lamivudine. ... 

Figure 9.14 The effective permeabilities (Pefr, different clinically relevant concentrations to mean SD) of cimetidine in human jejunum at investigate saturation in any carrier-mediated two clinically relevant luminal concentrations. transport across the intestinal epithelium. No The rate and extent of intestinal absorption of difference in Pefr values between the two cimetidine have been widely discussed, and Fa concentrations was noted, and, togetherwith the for this drug has been estimated at around observation that human permeability in vivo is 75% [90, 91], It has been reported that cimetidine similar to permeability in the Caco-2 model (with is a substrate for both P-gp and/or organic cation low expression of carrier proteins), this suggests transporters (OCNT1 and OCNT2) [82, 92], We that passive diffusion is the dominant determined the human jejunal in vivo Pe - at two mechanism even for cimetidine [82],...

Although cimetidine is an organic cation, it is a substrate that is recognized by both organic cation and anion transporters. PAH, methotrexate, estrone sulfate, prostaglandin, DHEAS... 

Probenecid markedly increased the AUC of the active metabolite of oseltamivir, but because of the large safety margin of oseltamivir, this increase is not considered to be clinically relevant. " Oseltamivir did not alter amoxicillin pharmacokinetics, and is therefore unlikely to interact with other renally secreted organic acids. Other drugs that are involved in the active anionic tubular secretion mechanism are also unlikely to interact. Cimetidine does not interact with oseltamivir, and other drugs that are inhibitors of the renal cationic secretion transport process are unlikely to interact. ... 

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