Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E.
Many childhood recipients of liver transplantation require massive doses of cyclosporin to achieve therapeutic blood concentrations of the drug. The impaired absorption of this strongly lipophilic drug may be due to reduced intestinal absorptive area, suboptimal mixing of the drug with hepatobiliary secretions, or residual cholestasis. Improvement of cyclosporin absorption was sought by means of oral coadministration of d-alpha-tocopheryl-polyethylene-glycol-1000 succinate (TPGS), a water-soluble form of vitamin E which can form micelles. 25 mg/kg daily of TPGS was given to six paediatric liver transplant recipients and one young adult with severe hepatobiliary graft-vs-host disease after bone-marrow transplantation, who required 29-136 mg/kg cyclosporin daily to achieve therapeutic cyclosporin blood concentrations. Five responded; the oral cyclosporin dose could be reduced by 40-72% within 2 months. In addition, intravenous cyclosporin was stopped in two of the responders. In the two non-responders the cyclosporin doses at entry were similar to those in the responders after TPGS treatment. Oral cyclosporin absorption tests correctly predicted the outcome of treatment in three responders and one non-responder tested. Treatment with TPGS to enhance cyclosporin absorption might be a useful way of reducing the high cost of immunosuppression in paediatric liver transplant recipients.
Sokol
R J
RJ
Department of Pediatrics, University of Colorado School of Medicine, Denver.
Johnson
K E
KE
Karrer
F M
FM
Narkewicz
M R
MR
Smith
D
D
Kam
I
I
D000328:Adult; D002648:Child; D002675:Child, Preschool; D003524:Cyclosporins / Q000493:pharmacokinetics*; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D007408:Intestinal Absorption / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008107:Liver Diseases / Q000097:blood / Q000378:metabolism / Q000601:surgery; D016031:Liver Transplantation; D011092:Polyethylene Glycols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use
D003524:Cyclosporins; D008055:Lipids; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan