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Effect of bile on cyclosporin absorption in liver transplant patients.

Mehta, M and Venkataramanan, R and Burckart, G and Ptachcinski, R and Delamos, B and Stachak, S and Van Thiel, D and Iwatsuki, S and Starzl, T (1988) Effect of bile on cyclosporin absorption in liver transplant patients. British Journal of Clinical Pharmacology, 25 (5). 579 - 584. ISSN 0306-5251

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1. We quantitated the effect of biliary diversion on cyclosporin (CyA) absorption in liver transplant patients. Multiple blood samples were obtained over one dosing interval following oral CyA administration in eight liver transplant patients before and after T‐tube clamping. 2. Cyclosporin concentrations were measured by a high pressure liquid chromatographic method. 3. The mean (+/‐ s.d.) dose‐normalized area under the blood concentration vs time curve (AUC) over a dosing interval was 5.23 (+/‐ 3.22) ng ml‐1 h during the pre clamping period and 15.79 +/‐ 7.92 ng ml‐1 h during the post clamping period. A significant (P less than 0.05) increase (276%) in the dose normalized AUC was observed following the T‐tube clamping. 4. Analysis of bile revealed less than 1 mg (less than 1% of dose) of unchanged CyA to be eliminated in bile over 12 h. Therefore the increased CyA AUC/dose following T‐tube ligation cannot be explained by enterohepatic recirculation. 5. Increased bile flow secondary to clamping of the T‐ tube most likely increased the absorption of CyA. Increase in CyA absorption may be due to a bile mediated increase in CyA solubility or gastrointestinal membrane permeability, or increased residence time at the site of absorption. 6. Independent of the mechanism involved, our results indicate that adjustments in CyA dosage must be made whenever external bile diversion is instituted or discontinued. 1988 The British Pharmacological Society


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Mehta, M
Venkataramanan, Rrv@pitt.eduRV
Burckart, G
Ptachcinski, R
Delamos, B
Stachak, S
Van Thiel, D
Iwatsuki, S
Starzl, Ttes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1988
Date Type: Publication
Journal or Publication Title: British Journal of Clinical Pharmacology
Volume: 25
Number: 5
Page Range: 579 - 584
DOI or Unique Handle: 10.1111/j.1365-2125.1988.tb03348.x
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0306-5251
Other ID: uls-drl:31735062129717, Starzl CV No. 820
Date Deposited: 08 Apr 2010 17:14
Last Modified: 02 Feb 2019 14:56


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