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 language||English (US)|
|Number of pages||6|
|Issue number||2 SUPPL. 2|
|State||Published - Jan 1 1988|
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