JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ochs, H. R.
Right arrow Articles by Hahn, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ochs, H. R.
Right arrow Articles by Hahn, N.

Hepatic vs. gastrointestinal presystemic extraction of oral midazolam and flurazepam

HR Ochs, DJ Greenblatt, W Eichelkraut, C Bakker, R Gobel and N Hahn

Medizinische und Chirurgische Universitatskliniken, University of Bonn, Federal Republic of Germany.

An experimental model was developed to elucidate the site of presystemic extraction of drugs with incomplete bioavailability due to high extraction after p.o. dosage. Domestic pigs received single i.v. or p.o. doses of midazolam (1 mg/kg) or flurazepam (2 mg/kg), two benzodiazepine derivatives with high presystemic extraction after p.o. dosage. Multiple blood samples were simultaneously drawn from the portal vein and from a systemic vein during 8 hr after dosage. After i.v. administration, both drugs had high systemic serum clearance, averaging 24 ml/min/kg. Area under the serum concentration curve (AUC) for systemic vs. portal sites was nearly identical for midazolam (769 vs. 737 ng/ml x hr); for flurazepam, systemic AUC exceeded portal AUC (1035 vs. 778 ng/ml x hr, P less than .01). After p.o. dosage, the systemic/portal AUC ratio averaged 0.15 for midazolam and 0.11 for flurazepam; for both drugs, portal AUC after p.o. dosage did not differ significantly from systemic AUC after i.v. administration. Thus, the extensive presystemic extraction of orally administered midazolam and flurazepam are mainly attributable to hepatic biotransformation rather than metabolism either within the gastrointestinal tract or during absorption into the portal circulation.

Volume 243, Issue 3, pp. 852-856, 12/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
V. P. Hosagrahara, L. K. Hansen, and R. P. Remmel
Induction of the Metabolism of Midazolam by Rifampin in Cultured Porcine Hepatocytes: Preliminary Evidence for CYP3A Isoforms in Pigs
Drug Metab. Dispos., December 1, 1999; 27(12): 1512 - 1518.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
W. Jacobsen, G. Kirchner, K. Hallensleben, L. Mancinelli, M. Deters, I. Hackbarth, K. Baner, L. Z. Benet, K.-F. Sewing, and U. Christians
Small Intestinal Metabolism of the 3-Hydroxy-3-methylglutaryl-Coenzyme A Reductase Inhibitor Lovastatin and Comparison with Pravastatin
J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 131 - 139.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Lampen, Y. Zhang, I. Hackbarth, L. Z. Benet, K.-Fr. Sewing, and U. Christians
Metabolism and Transport of the Macrolide Immunosuppressant Sirolimus in the Small Intestine
J. Pharmacol. Exp. Ther., June 1, 1998; 285(3): 1104 - 1112.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.