Effect of inflammatory bowel disease on absorption and disposition of prednisolone

Milsap, Rebecca L.; George, Donald E.; Szefler, Stanley J.; Murray, Kathleen A.; Lebenthal, Emanuel; Jusko, William J.

doi:10.1007/bf01315146

Cited by 29 publications

(18 citation statements)

References 25 publications

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“…No significant impairment of absorption occurred during either active disease or remission in adolescent patients. Similar findings are seen in patients with acute colitis (Elliot et al 1980) and Cmax was lower after oral than after intravenous administration (Milsap et al 1983). Similar findings are seen in patients with acute colitis (Elliot et al 1980) and Cmax was lower after oral than after intravenous administration (Milsap et al 1983).…”

Section: Corticosteroidssupporting

confidence: 74%

“…Furthermore, the consequences of the disease process itself on drug disposition and elimination may outweigh its etTects on absorption (Elliot et al 1980;Milsap et al 1983;Tanner et al 1981). Diseases such as inflammatory bowel disease (IBD) and coeliac disease, which affect the mucosal surface of the intestinal lumen or the gastric emptying time, have variable etTects on drug absorption.…”

Section: Effect Of Gastrointestinal Disease On Drug Absorptionmentioning

confidence: 99%

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Drug Absorption in Gastrointestinal Disease and Surgery

Gubbins

Bertch

1991

Clinical Pharmacokinetics

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Drug absorption from the gastrointestinal (GI) tract and the impact of GI surgery and disease on drug absorption are discussed. Recommendations are made to manage problems of drug malabsorption. Absorption from the GI tract is a first-order process described by its rate and extent. GI surgery changes the anatomy of the GI tract and alters important variables in the absorption process. In the wake of procedures which diminish small bowel surface area, the extent of absorption of phenytoin, digoxin, cyclosporin, aciclovir, hydrochlorothiazide and certain oral contraceptives is reported to be reduced. The underlying cause of the reduction is unknown. When gastric emptying time or pH are altered by surgery, the rate of drug absorption appears to be reduced. However, it is not clear which variable is more important in determining therapeutic effects. The effects of coeliac and inflammatory bowel diseases on the distribution and clearance of drugs must be considered before attributing abnormal serum concentrations of drugs to malabsorption. GI disease may slow gastric emptying and delay the complete absorption of drugs when their rate of absorption depends on gastric emptying time. Other inflammatory GI diseases such as graft-versus-host disease (GVHD) of the gut, Behçet's syndrome and scleroderma involving the GI tract may directly reduce absorption of drugs such as cyclosporin, amitriptyline, benzodiazepines, anticonvulsants, paracetamol (acetaminophen) and penicillamine. GI diseases which alter gut pH affect the absorption only of drugs with limited water solubility and pH-dependent dissolution such as ketoconazole. Clinicians should be aware of the variable absorption seen after GI disease and surgery and monitor their patients accordingly.

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Section: Corticosteroidssupporting

confidence: 74%

Section: Effect Of Gastrointestinal Disease On Drug Absorptionmentioning

confidence: 99%

Drug Absorption in Gastrointestinal Disease and Surgery

Gubbins

Bertch

1991

Clinical Pharmacokinetics

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“…38 Low albumin levels have repeatedly been associated with reduced protein binding and increased glucocorticoid side effects, [39][40][41][42] as seen in celiac disease, 39 systemic lupus erythematosus, 41 and inflammatory bowel disease. 42 Moreover, liver 9,10 and renal 36,37 failure, with or without hypoalbuminemia, have both been associated with increased exposure to unbound prednisolone. Unbound prednisolone concentrations are also increased in renal transplant patients, primarily due to reduced renal or hepatic clearance, 43 and similar findings have been made in liver or lung transplant recipients.…”

Section: Discussionmentioning

confidence: 98%

Role of Prednisolone Pharmacokinetics in Postchallenge Glycemia After Renal Transplantation

Bergrem¹,

Hartmann²,

Hjelmesaeth³

et al. 2008

Therapeutic Drug Monitoring

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Prednisolone may cause hyperglycemia after organ transplantation. Even at comparable weight-adjusted doses, prednisolone side effects vary considerably between individuals, suggesting between-patient pharmacokinetic differences. In renal transplant patients, assessment of glucocorticoid diabetogenicity is confounded by calcineurin inhibitors (CNIs). The present study aimed to investigate, in a CNI-free setting, the association between exposure to unbound prednisolone and glucose tolerance in stable nondiabetic long-term renal transplant patients. An oral glucose tolerance test and a 12-hour prednisolone pharmacokinetic study were performed in 108 nondiabetic CNI-naive subjects (41 women and 67 men) treated with prednisolone (median 0.15 mg kg d, interquartile range 0.14-0.18 mg kg d) and azathioprine. The area under the curve (AUC) of unbound prednisolone was analyzed in multiple linear regression analysis with 120-minute postchallenge glucose AUC as the dependent variable. A high AUC of unbound serum prednisolone was independently associated with a high glucose AUC (P = 0.030). A high glucose AUC was also associated with a high patient age and triglyceride level (both P < or = 0.001). No correlation was observed between the daily prednisolone dosage (mg/d or mg kg d) and glucose AUC. The association between exposure to unbound prednisolone and postchallenge glycemia is in line with current knowledge about mechanisms behind steroid-related side effects but has not previously been documented. The result may argue in favor of measuring unbound prednisolone in clinical settings. Increasing exposure to unbound prednisolone was independently associated with postchallenge glycemia. No such relationship was observed for prednisolone daily dose per se.

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“…Higher doses of prednisone saturate the binding to transcortin, and proportionally more unbound prednisolone will be present, resulting in an increased total clearance. For IBD patients, protein binding is decreased in patients with active disease compared with remission, probably due to decreased plasma albumin concentrations in active disease [51].…”

Section: Pharmacokinetic and Pharmacodynamic Considerationsmentioning

confidence: 99%

“…It has a low systemic bioavailability (10%) and thereby exhibits lower systemic toxicity compared with prednisone [19,[52][53][54][55][56]. Budesonide has shown to be efficacious and safe in the treatment of UC [49][50][51]. It is metabolized in the liver via the cytochrome P450 (CYP) 3A4 system into two pharmacologically inactive metabolites, which are primarily excreted via the kidneys [52,53].…”

Section: Pharmacokinetic and Pharmacodynamic Considerationsmentioning

confidence: 99%