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First-pass Metabolism Of Cyclosporin By The Gut
J. Kolars, P. Watkins, R. Merion, W. Awni
Published 1991 · Medicine
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Cyclosporin is thought to be exclusively metabolised in the liver. We instilled cyclosporin into the small bowel of 2 patients during the anhepatic phase of liver transplantation; cyclosporin metabolites were readily detected in portal venous blood. Our findings indicate that the small intestine is a major site of cyclosporin breakdown: such intestinal metabolism might help to explain the poor oral bioavailability and drug interactions of cyclosporin.
This paper references
Drug therapy: cyclosporine
B. Kahan (1989)
Body weight control: The physiology, clinical treatment, and prevention of obesity
A. Bender (1987)
Effects of repeated fenfluramine administration on indices of monoamine function in rat brain: pharmacokinetic, dose response, regional specificity and time course data.
R. Zaczek (1990)
Cyclosporin-erythromycin interaction in renal transplant patients.
S. K. Gupta (1989)
D-, L- and DL-fenfluramine cause long-lasting depletions of serotonin in rat brain
M. Kleven (1989)
Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine.
T. Aoyama (1989)
Species differences in the kinetics and metabolism of fenfluramine isomers.
S. Caccia (1982)
Cyclosporin toxicity at therapeutic blood levels and cytochrome P-450 IIIA
M. R. Lucey (1990)
Clinical Pharmacokinetics of Cyclosporin
R. Ptachcinski (1986)
Cyclosporine metabolism in human liver: Identification of a cytochrome P‐450III gene family as the major cyclosporine‐metabolizing enzyme explains interactions of cyclosporine with other drugs
T. Kronbach (1988)
Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man.
P. Watkins (1987)
CYCLOSPORINE METABOLISM BY P450IIIA IN RAT ENTEROCYTES—ANOTHER DETERMINANT OF ORAL BIOAVAILABILITY?
J. Kolars (1992)
5-hydroxytryptamine in psychiatry : a spectrum of ideas
M. Sandler (1991)
Optimized high-performance liquid chromatographic method for the analysis of cyclosporine and three of its metabolites in blood and urine.
W. Awni (1988)
Anorexigenic effects of fenfluramine hydrochloride in rats, guinea pigs, and dogs.
R. S. Alphin (1969)
Role of cytochromes P450 in drug metabolism and hepatotoxicity.
P. Watkins (1990)
INTERNATIONAL TRIAL OF LONG-TERM DEXFENFLURAMINE IN OBESITY
B. Guy-grand (1989)
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The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine
D. Gómez (1995)
Gender Effects in Pharmacokinetics and Pharmacodynamics
R. Z. Harris (2012)
Erythromycin‐felodipine interaction: Magnitude, mechanism, and comparison with grapefruit juice
D. Bailey (1996)
Absence of correlations among three putative in vivo probes of human cytochrome P4503A activity in young healthy men
M. Kinirons (1993)
Cytochrome P-450 1A1 expression in human small bowel: interindividual variation and inhibition by ketoconazole.
M. Paine (1999)
The Oral Route for the Administration of Cytotoxic Drugs: Strategies to Increase the Efficiency and Consistency of Drug Delivery
H. A. Bardelmeijer (2004)
Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4
R. K. Bhardwaj (2002)
In vitro and in vivo evaluations of the metabolism, pharmacokinetics, and bioavailability of ester prodrugs of L-767,679, a potent fibrinogen receptor antagonist: an approach for the selection of a prodrug candidate.
T. Prueksaritanont (1997)
Prediction of cyclosporine clearance in liver transplant recipients by the use of midazolam as a cytochrome P450 3A probe
J. Villeneuve (2000)
Intestinal drug transporters: an overview.
M. Estudante (2013)
Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin
M. Fromm (1996)
Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans
H. Glaeser (2004)
Regional Proteomic Quantification of Clinically Relevant Non-Cytochrome P450 Enzymes along the Human Small Intestine
H. Zhang (2020)
Intestinal clearance of H2-antagonists.
Y. Hui (1994)
Study on herb-drug interactions
L. Yang (2009)
An update on the potential role of intestinal first-pass metabolism for the prediction of drug–drug interactions: the role of PBPK modeling
Saeed Alqahtani (2018)
Current trends in
V. Zawar (2010)
First-pass metabolism of midazolam by the human intestine.
M. Paine (1996)
Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity.
Q. Wu (2019)
A Critical Review of Cyclosporine Therapy in Inflammatory Bowel Disease
W. Sandborn (1995)
Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine
C. M. Stein (1996)
Molecular mechanisms of drug metabolism in the critically ill.
G. Park (1996)
Inhibition of Nifedipine Metabolism in Dogs by Erythromycin: Difference between the Gut Wall and the Liver
S. Tsuruta (1997)
Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism.
M. Paine (1997)
Situations with enhanced chemical risks due to toxicokinetic and toxicodynamic factors.
E. Dybing (1999)
Effects of the Antifungal Agents on Oxidative Drug Metabolism
K. Venkatakrishnan (2000)
Effects of gemfibrozil and rifampicin on the pharmacokinetics of HMG-CoA reductase inhibitors
C. Kyrklund (2004)
Drug metabolism in human and rat intestine: an 'in vitro' approach
E. G. V. D. Kerkhof (2007)
PLGA nanoparticles for oral delivery of cyclosporine: nephrotoxicity and pharmacokinetic studies in comparison to Sandimmune Neoral.
J. L. Italia (2007)
Differentiation of absorption and first‐pass gut and hepatic metabolism in humans: Studies with cyclosporine
C. Wu (1995)
Metabolism of lidocaine by rat pulmonary cytochrome P450.
K. Tanaka (1994)
Enantiomeric cyclic peptides with different Caco-2 permeability suggest carrier-mediated transport.
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