Presystemic elimination of budesonide in man when administered locally at different levels in the gut, with and without local inhibition by ketoconazole

European Journal of Pharmaceutical Sciences

Volumn 35, Issue 4, 2008, Pages 264-270

  Seidegård, Janeric ^a   Nyberg, Lars ^b   Borgå, Olof ^b  

^a ASTRAZENECA R AND D   (Sweden)

^b Bioperm AB   (Sweden)

Author keywords

Budesonide; Colon; CYP3A; First pass metabolism; Intubation; Small intestine

Indexed keywords

BUDESONIDE; CYTOCHROME P450 3A4; DEUTERIUM; KETOCONAZOLE; METOCLOPRAMIDE; TECHNETIUM 99M;

ADULT; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG ELIMINATION; DRUG METABOLISM; ENZYME ACTIVITY; FIRST PASS EFFECT; HUMAN; HUMAN EXPERIMENT; INTESTINE WALL; MALE; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; STOMACH INTUBATION;

ADULT; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIFUNGAL AGENTS; AREA UNDER CURVE; BUDESONIDE; COLON; CYTOCHROME P-450 CYP3A; DOUBLE-BLIND METHOD; DRUG INTERACTIONS; ENZYME INHIBITORS; HUMANS; ILEUM; INTUBATION, GASTROINTESTINAL; JEJUNUM; KETOCONAZOLE; MALE; YOUNG ADULT;

EID: 54049086058     PISSN: 09280987     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejps.2008.07.005     Document Type: Article

References (22)

1. Edsbäcker S., and Andersson T. Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease. Clin. Pharmacokinet. 43 (2004) 803-821
2. Edsbäcker S., Bengtsson B., Larsson P., Lundin P., Ulmius J., and Wollmer P. A pharmacoscintigraphic evaluation of oral budesonide given as controlled-release (Entocort) capsules Aliment. Pharmacol. Ther. 17 (2003) 525-536
3. Fojo A.T., Ueda K., Slamon D.J., Poplack D.G., Gottesman M.M., and Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc. Natl. Acad. Sci. U.S.A. 84 (1987) 265-269
4. Fromm M.F., Busse D., Kroemer H.K., and Eichelbaum M. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology 24 (1996) 796-801
5. Hall S.D., Thummel K.E., Watkins P.B., Lown K.S., Benet L.Z., Paine M.F., Mayo R.R., Turgeon D.K., Bailey D.G., Fontana R.J., and Wrighton S.A. Molecular and physical mechanisms of first-pass extraction. Drug. Metab. Dispos. 27 (1999) 161-166
6. Hebert M.F., Roberts J.P., Prueksaritanont T., and Benet L.Z. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin. Pharmacol. Ther. 52 (1992) 453-457
7. Holtbecker N., Fromm M.F., Kroemer H.K., Ohnhaus E.E., and Heidemann H. The nifedipine-rifampin interaction Evidence for induction of gut wall metabolism. Drug Metab. Dispos. 24 (1996) 1121-1123
8. Jönsson G., Åström A., and Andersson P. Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver. Drug. Metab. Dispos. 23 (1995) 137-142
9. Kolars J.C., Awni W.M., Merion R.M., and Watkins P.B. First-pass metabolism of cyclosporin by the gut. Lancet 338 (1991) 1488-1490
10. Kolars J.C., Schmiedlin-Ren P., Schuetz J.D., Fang C., and Watkins P.B. Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J. Clin. Invest. 90 (1992) 1871-1878
11. Lin Y.S., Dowling A.L., Quigley S.D., Farin F.M., Zhang J., Lamba J., Schuetz E.G., and Thummel K.E. Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Mol. Pharmacol. 62 (2002) 162-172
12. Lown K.S., Kolars J.C., Thummel K.E., Barnett J.L., Kunze K.L., Wrighton S.A., and Watkins P.B. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test. Drug. Metab. Dispos. 22 (1994) 947-955
13. Nyberg L., Månsson W., Abrahamsson B., Seidegård J., and Borgå O. A convenient method for local administration at predefined sites in the entire gastrointestinal tract: experiences from 13 phase I studies. Eur. J. Pharm. Sci. 30 (2007) 432-440
14. Paine M.F., Shen D.D., Kunze K.L., Perkins J.D., Marsh C.L., McVicar J.P., Barr D.M., Gillies B.S., and Thummel K.E. First-pass metabolism of midazolam by the human intestine. Clin. Pharmacol. Ther. 60 (1996) 14-24
15. Paine M.F., Khalighi M., Fisher J.M., Shen D.D., Kunze K.L., Marsh C.L., Perkins J.D., and Thummel K.E. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J. Pharmacol. Exp. Ther. 283 (1997) 1552-1562
16. Ryrfeldt A., Edsbäcker S., and Pauwels R. Kinetics of the epimeric glucocorticoid budesonide. Clin. Pharmacol. Ther. 35 (1984) 525-530
17. Seidegård J. Reduction of the inhibitory effect of ketoconazole on budesonide pharmacokinetics by separation of their time of administration. Clin. Pharmacol. Ther. 68 (2000) 13-17
18. Thummel K.E., O'Shea D., Paine M.F., Shen D.D., Kunze K.L., Perkins J.D., and Wilkinson G.R. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin. Pharmacol. Ther. 59 (1996) 491-502
19. Wacher V.J., Silverman J.A., Zhang Y.C., and Benet L.Z. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J. Pharm. Sci. 87 (1998) 1322-1330
20. Washington N., Washington C., and Wilson C.G. Physiological Pharmaceutics. Barriers to drug absorption. 2nd ed. (2001), Taylor & Francis, London p. 117
21. Wu C.-Y., Benet L.Z., Hebert M.F., Gupta S.K., Rowland M., Gomez D.Y., and Wacher W.J. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin. Pharmacol. Ther. 58 (1995) 492-497
22. Zhang Q.-Y., Dunbar D., Ostrowska A., Zeisloft S., Yang J., and Kaminsky L.S. Characterization of human small intestinal cytochromes P-450. Drug. Metab. Dispos. 27 (1999) 804-809