Interaction by Cholestyramine on the Uptake of Hydrocortisone in the Gastrointestinal Tract

Abstract

ABSTRACT. An absolute reduction of the plasma cortisol levels and a delay of the peak concentrations were recorded in 10 healthy subjects, when a bile‐sequestering anionic exchange resin, cholestyramine, was given prior to a single oral hydrocortisone dose, indicating that the resin interferes with the uptake of a neutral sterol in the human gastrointestinal tract. The possibility of a direct binding of drug to resin is supported by the affinity of hydrocortisone to cholestyramine in vitro, which was uninfluenced by the presence of sodium taurocholate. Cholestyramine significantly delayed the gastric emptying of a glucose solution, indicating that the resin not only decreases but also delays hydrocortisone absorption. Careful supervision is recommended when treatment with cholestyramine is given concomitant to neutral sterol drugs.

Effect of the Bile Acid Sequestrant Colesevelam on the Pharmacokinetics of Pioglitazone, Repaglinide, Estrogen Estradiol, Norethindrone, Levothyroxine, and Glyburide

“…The drug interaction potential for colesevelam is considered low compared to that for conventional BA sequestrants. This is based on the observation that, although many drugs have been shown to interact with the conventional BA sequestrants (eg, fluvastatin, 19 digoxin, 27 warfarin, 28 glipizide, 29 hydrochlorothiazide, 30 propanolol, 31 frusemide, 32 ezetimibe, 33 hydrocortisone, 34 diclofenac, 35 sulindac, 36 and valproate 37 ), pharmacokinetic studies demonstrated that colesevelam does not interact with any of the drugs tested (digoxin, metoprolol, quinidine, valproic acid, warfarin, fenofibrate, lovastatin, and verapamil) 21 – 23 with the possible exception of verapamil. Importantly, this list includes some of the same drugs that did show an interaction with conventional BA sequestrants (ie, digoxin, warfarin, and valproate) 23 .…”

Binding interactions with sevelamer and polystyrene sulfonate in vitro

“…In vitro experiments, to assess binding to resins, have been described in literature before. 21 , 23 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 The sensitivity of in vitro studies for identifying compounds binding to resins is high, but the specificity may be low. 32 Studies confirming that in vitro binding is also clinically relevant in vivo have been described for different drug–resin combinations.…”

“… 32 Studies confirming that in vitro binding is also clinically relevant in vivo have been described for different drug–resin combinations. 21 , 22 , 32 , 39 , 40 , 42 , 43 However, there are also several studies in which in vitro binding could not be confirmed in vivo to the same extent. 32 , 34 , 36 , 41 , 44 , 45 , 46 This can be explained by the fact that drug absorption from the gastrointestinal tract is affected by many different factors such as absorptive surface area, pH, food effects, co‐medication, intestinal transit time, passive intestinal permeability, intestinal transporters, and enzymes that are not accounted for in vitro .…”

“…In vitro experiments, to assess binding to resins, have been described in literature before 21,23,32,34‐43 . The sensitivity of in vitro studies for identifying compounds binding to resins is high, but the specificity may be low 32 .…”

Sodium cholate sorption on N-octadecylpectinamide in comparison with cholestyramine

“…Owing to its interrupting the enterohepatic circulation of bile acids, cholestyramine increases their faecal excretion and triggers a compensatory increase in the cholesterol oxidation in the liver. However, this polymeric resin also binds anionic drugs, vitamins, and salts ( Johansson et al 1978;Harmon & Seifert 1991). The competition for cholestyramine binding sites in the digestive tract decreases the binding capacity for bile acids, so large doses are required for the effective sorption (Stedronsky 1994).…”