Cimetidine Alfentanil

For weak acids, e.g., salicylic acid, the dependency on a pH gradient becomes complex since both the passive diffusion and the active transport process will be dependent on the proton concentration in the apical solution [61, 63, 98, 105] and a lowering of the pH from 7.4 to 6.5 will increase the apical to basolateral transport more than 20-fold. Similarly, for weak bases such as alfentanil or cimetidine, a lowering of the pH to 6.5 will decrease the passive transport towards the basolateral side [105]. The transport of the ionizable compound will, due to the pH partition hypothesis, follow the pKa curve. 

In a study of the permeability of alfentanil and cimetidine through Caco-2 cells, a model for oral absorption, it was deduced that at pH 5 about 60 % of the cimetidine transport and 17 % of the alfentanil transport across Caco-2 monolayers can be attributed to the ionized form [16] (Figure 1.3). Thus the dogma that only neutral species can cross a membrane has been challenged recently. 

Fig. 1.3 Transportation rate of basic drugs across Caco-2 monolayers alfentanil, rapid transport cimetidine, slow transport [16].

Drugs that may affect fluconazole include cimetidine, hydrochlorothiazide, and rifampin. Drugs that may be affected by fluconazole include alfentanil, benzodiazepines, buspirone, carbamazepine, cisapride, oral contraceptives, corticosteroids, cyclosporine, haloperidol, HMG-CoA reductase inhibitors, losartan, nisoldipine, phenytoin, protease inhibitors, rifabutin, sirolimus, sulfonylureas, tacrolimus, theophylline, tolterodine, tricyclic antidepressants, vinca alkaloids, warfarin, zidovudine, and zolpidem. 

ALFENTANIL, FENTANYL, PETHIDINE, TRAMADOL CIMETIDINE Cimetidine may t fentanyl, pethidine and tramadol levels Cimetidine inhibits CYP2D6-medi-ated metabolism of these opioids. Ranitidine weakly inhibits CYP2D6 Watch for excessive narcotization... 

The CYP3A4 isozyme is responsible for the metabolism of a large number of endogenous compounds as well as a wide range of drugs (50). Fentanyl, alfentanil, and sufentanil are substrates for CYP3A4, and therefore drugs that inhibit this enzyme, such as erythromycin, HIV protease inhibitors, or cimetidine. 

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