Mannitol Cyclosporine

Figure 3 Correlation between the fraction absorbed and the membrane permeability in Caco-2 cells. Papp represents the membrane permeability of following 20 compounds, and was obtained by measuring the transcellular transport from the apical-to-basal side in Caco-2 cells. The fraction absorbed was obtained from literature. A amoxicillin, B antipyrine, C atenolol, D caffein, E cephalexin, F cyclosporin A, G enalaprilate, H L-glutamine, I hydrocortisone, J inulin, K D-mannitol, L metoprolol, M L-phenylalanine, N PEG-400, O PEG-4000, P propranolol, Q sucrose, R taurocholate, S terbutaline, T testosterone. Source From Ref. 37.

The transport-enhancing effect of Zot was shown to be reversible and nontoxic (Fasano et al. 1991 Cox et al. 2002). More recently a smaller fragment of Zot in the size of 12 kDa referred to as /1G was identified (Di Pierro et al. 2001). AG displayed significant potential as permeation enhancer. In vitro studies showed that it is capable of significantly increasing the apparent permeability coefficients for a wide variety of drugs across Caco-2 monolayer (Salama et al. 2003, 2004). In the presence of peptidase inhibitors AG improved the bioavailability of mannitol, inulin and PEG 4000 after intraduodenal administration to rats (Salama et al. 2003, 2004). In another in vivo study the oral bioavailability of cyclosporin A was increased up to 50-fold due to the co-administration of AG when metabolic protection was provided (Salama et al. 2005). Results of this study are illustrated in Fig. 5.2. 

Figure 6.3 Plot of the fraction of dose absorbed (in %) of various drugs as a function of the permeability estimates in the Caco-2 system. Key 1 D-glucose 2 verapamil 3 piroxicam 4 phenylalanine 5 cyclosporin 6 enalapril 7 cephalexim 8 losartan 9 lisinopril 10 amoxicillin 11 methyldopa 12 naproxen 13 an-tipyrine 14 desipramine 15 propanolol 16 amiloride 17 metoprolol 18 terbu-taline 19 mannitol 20 cimetidine 21 ranitidine 22 enalaprilate 23 atenolol 24 hydrochlorothiazide.

Nephrotoxicity is best minimized by limiting the cumulative dose and avoiding concomitant administration of other nephrotoxins, particularly cyclosporine. Additionally, providing hydration with a high sodium diet and 1 L intravenous 0.9% sodium chloride daily appears to reduce toxicity. Mannitol infusion to induce an osmotic diuresis has not been protective. Lastly, several liposomal amphotericin B formulations are now available and have been reported to reduce nephrotoxicity by enhancing drug delivery to sites of infection and thereby reducing exposure of mammalian cell membranes. ... 

NSAIDs, glafenin, contrast media, acetaminophen, cyclosporine, cisplatin, IV immune globulin, dextran, maltose, sucrose, mannitol, heavy metals. 

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