The effect of Roux-en-Y biliary enterostomy on the absorption of cyclosporine: Relevance to poor drug bioavalability in children after orthotopic liver transplantation

B. H. Kehrer, P. F. Whitington, Dennis Black

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

CsA bioavailability is particularly poor in children after OLT. In our own patients, the dosage required to maintain therapeutic blood levels in children ranges from 9 to 218 mg/kg/d (47.6 ± 54.2 SD), wehreas in adults it ranges from 1 to 8 mg/kg/d (4.4 ± 1.7). This is in part due to rapid clearance as is evidenced by somewhat increased needs of children with kidney and bone marrow transplants relative to adults. However, the degree of increased clearance does not seem adequate to explain the many-fold reduced bioavailability in children. We speculate that reduced absorption also plays a role. Most pediatric patients who require OLT have biliary atresia; others have ducts too small to allow duct-to-duct anastomosis. Therefore, in most children, a Roux-en-Y is constructed, and the donor bile duct is anastomosed to the Roux-loop. This results in (1) shortening of the bowel in continuity and (2) mixture of bile with bowel contents relatively distally. The former would reduce the total surface area available for absorption and the latter would reduce CsA absorption because of its dependence on bile salts. Our hypothesis is that the Roux-en-Y choledocho-jejunostomy used in OLT in children as a major factor in poor Csa absorption in this group. The simulation of this circumstance in the laboratory rat is the basis of these experiments.

Original languageEnglish (US)
Pages (from-to)523-528
Number of pages6
JournalTransplantation Proceedings
Volume20
Issue number2 SUPPL. 2
StatePublished - Jan 1 1988
Externally publishedYes

Fingerprint

Enterostomy
Liver Transplantation
Cyclosporine
Pharmaceutical Preparations
Biological Availability
Jejunostomy
Biliary Atresia
Bile Ducts
Bile Acids and Salts
Bile
Bone Marrow
Tissue Donors
Pediatrics
Transplants
Kidney

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

The effect of Roux-en-Y biliary enterostomy on the absorption of cyclosporine : Relevance to poor drug bioavalability in children after orthotopic liver transplantation. / Kehrer, B. H.; Whitington, P. F.; Black, Dennis.

In: Transplantation Proceedings, Vol. 20, No. 2 SUPPL. 2, 01.01.1988, p. 523-528.

Research output: Contribution to journalArticle

@article{6cc8df34a27a400a9b11dc1628092ebc,
title = "The effect of Roux-en-Y biliary enterostomy on the absorption of cyclosporine: Relevance to poor drug bioavalability in children after orthotopic liver transplantation",
abstract = "CsA bioavailability is particularly poor in children after OLT. In our own patients, the dosage required to maintain therapeutic blood levels in children ranges from 9 to 218 mg/kg/d (47.6 ± 54.2 SD), wehreas in adults it ranges from 1 to 8 mg/kg/d (4.4 ± 1.7). This is in part due to rapid clearance as is evidenced by somewhat increased needs of children with kidney and bone marrow transplants relative to adults. However, the degree of increased clearance does not seem adequate to explain the many-fold reduced bioavailability in children. We speculate that reduced absorption also plays a role. Most pediatric patients who require OLT have biliary atresia; others have ducts too small to allow duct-to-duct anastomosis. Therefore, in most children, a Roux-en-Y is constructed, and the donor bile duct is anastomosed to the Roux-loop. This results in (1) shortening of the bowel in continuity and (2) mixture of bile with bowel contents relatively distally. The former would reduce the total surface area available for absorption and the latter would reduce CsA absorption because of its dependence on bile salts. Our hypothesis is that the Roux-en-Y choledocho-jejunostomy used in OLT in children as a major factor in poor Csa absorption in this group. The simulation of this circumstance in the laboratory rat is the basis of these experiments.",
author = "Kehrer, {B. H.} and Whitington, {P. F.} and Dennis Black",
year = "1988",
month = "1",
day = "1",
language = "English (US)",
volume = "20",
pages = "523--528",
journal = "Transplantation Proceedings",
issn = "0041-1345",
publisher = "Elsevier USA",
number = "2 SUPPL. 2",

}

TY - JOUR

T1 - The effect of Roux-en-Y biliary enterostomy on the absorption of cyclosporine

T2 - Relevance to poor drug bioavalability in children after orthotopic liver transplantation

AU - Kehrer, B. H.

AU - Whitington, P. F.

AU - Black, Dennis

PY - 1988/1/1

Y1 - 1988/1/1

N2 - CsA bioavailability is particularly poor in children after OLT. In our own patients, the dosage required to maintain therapeutic blood levels in children ranges from 9 to 218 mg/kg/d (47.6 ± 54.2 SD), wehreas in adults it ranges from 1 to 8 mg/kg/d (4.4 ± 1.7). This is in part due to rapid clearance as is evidenced by somewhat increased needs of children with kidney and bone marrow transplants relative to adults. However, the degree of increased clearance does not seem adequate to explain the many-fold reduced bioavailability in children. We speculate that reduced absorption also plays a role. Most pediatric patients who require OLT have biliary atresia; others have ducts too small to allow duct-to-duct anastomosis. Therefore, in most children, a Roux-en-Y is constructed, and the donor bile duct is anastomosed to the Roux-loop. This results in (1) shortening of the bowel in continuity and (2) mixture of bile with bowel contents relatively distally. The former would reduce the total surface area available for absorption and the latter would reduce CsA absorption because of its dependence on bile salts. Our hypothesis is that the Roux-en-Y choledocho-jejunostomy used in OLT in children as a major factor in poor Csa absorption in this group. The simulation of this circumstance in the laboratory rat is the basis of these experiments.

AB - CsA bioavailability is particularly poor in children after OLT. In our own patients, the dosage required to maintain therapeutic blood levels in children ranges from 9 to 218 mg/kg/d (47.6 ± 54.2 SD), wehreas in adults it ranges from 1 to 8 mg/kg/d (4.4 ± 1.7). This is in part due to rapid clearance as is evidenced by somewhat increased needs of children with kidney and bone marrow transplants relative to adults. However, the degree of increased clearance does not seem adequate to explain the many-fold reduced bioavailability in children. We speculate that reduced absorption also plays a role. Most pediatric patients who require OLT have biliary atresia; others have ducts too small to allow duct-to-duct anastomosis. Therefore, in most children, a Roux-en-Y is constructed, and the donor bile duct is anastomosed to the Roux-loop. This results in (1) shortening of the bowel in continuity and (2) mixture of bile with bowel contents relatively distally. The former would reduce the total surface area available for absorption and the latter would reduce CsA absorption because of its dependence on bile salts. Our hypothesis is that the Roux-en-Y choledocho-jejunostomy used in OLT in children as a major factor in poor Csa absorption in this group. The simulation of this circumstance in the laboratory rat is the basis of these experiments.

UR - http://www.scopus.com/inward/record.url?scp=0023897948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023897948&partnerID=8YFLogxK

M3 - Article

C2 - 3284100

AN - SCOPUS:0023897948

VL - 20

SP - 523

EP - 528

JO - Transplantation Proceedings

JF - Transplantation Proceedings

SN - 0041-1345

IS - 2 SUPPL. 2

ER -