Small-bowel length and the dose of cyclosporine in children after liver transplantation.
Children, particularly infants, require large oral doses of cyclosporine to achieve immunosuppression after liver transplantation. In 53 children who had received liver transplants, we examined the relation of height, weight, residual small-bowel length, and (in 17 children) the terminal plasma clearance rate of cyclosporine to the dose of cyclosporine required to achieve blood levels of 200 ng per milliliter. The required intravenous dose of cyclosporine (expressed as milligrams per day) increased steeply as body size and bowel length increased, whereas the required oral dose declined with increasing bowel length. When expressed as milligrams per square meter of body-surface area per day, the required intravenous dose did not change with body size, but the required oral dose declined with increasing body size. Small-bowel length correlated closely and inversely with the log of the oral dose of cyclosporine (r = -0.77, P = 0.0001). The rate of clearance was also related to the log of the oral dose (r = 0.57, P = 0.017) but was independent of age and size. Multiple regression analyses that included height and weight showed that only small-bowel length and the rate of clearance from plasma were independently related to the required oral dose of cyclosporine. We concluded that the length of the small bowel is the chief determinant of the required dose of orally administered cyclosporine in children after liver transplantation. Children and infants require large oral doses of cyclosporine because of the limited absorptive surface area of their intestines.
Whitington
P F
PF
Department of Pediatrics, University of Chicago Pritzker School of Medicine, Wyler Children's Hospital, IL.
Emond
J C
JC
Whitington
S H
SH
Broelsch
C E
CE
Baker
A L
AL
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001827:Body Height; D001830:Body Surface Area; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003524:Cyclosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D007421:Intestine, Small / Q000033:anatomy & histology*; D016031:Liver Transplantation; D008657:Metabolic Clearance Rate; D012044:Regression Analysis
D003524:Cyclosporins