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PMID: 9195117 Published · ppublish English Journal Article Review

Cyclosporin pharmacokinetics in paediatric transplant recipients.

Clinical pharmacokinetics ·Vol. 32 ·No. 6 ·1997-06-00 ·Pages 481-95

Cooney GF, Habucky K, Hoppu K

Abstract

Cyclosporin is an essential component of the antirejection drug protocol used in the long term management of paediatric organ transplant recipients. This article looks at the pharmacokinetics of cyclosporin in paediatric kidney, heart, liver and bone marrow transplant recipients and critically evaluates its relationship to pharmacokinetic data in adult transplant recipients. There are limited data on the pharmacokinetics of cyclosporin in paediatric transplant recipients (14 publications provide the database) as compared with the adult transplant population. Study design, analytical methodology and age ranges of the individuals differ between studies, making comparative interpretation of pharmacokinetic data difficult. However, significant trends are noteworthy and these may influence dose administration guidelines and therapeutic monitoring standards for cyclosporin in the paediatric organ transplant recipient. The bioavailability of the oral formulations of cyclosporin is highly variable as with the adult population, but there appears to be a correlation between cyclosporin bioavailability and age with both the traditional oral formulation (Sandimmun) and the new microemulsion formulation (Neoral) in young liver transplant patients. Bowel length, presystemic metabolism in the gut wall, type of transplant and time since transplant are contributing factors in the variation of bioavailability patterns in paediatric transplant patients. The volume of distribution of cyclosporin does not appear to differ between paediatric and adult transplant recipients, but systemic clearance is comparatively higher in the paediatric population. In general, paediatric patients require higher doses of cyclosporin to achieve target blood concentrations of the drug which are equivalent to the values used in the adult population. Younger patients (less than 8 years of age) may be managed more effectively with a 3 times daily administration schedule rather than the twice daily schedule which is universally used for cyclosporin in the transplant population. The comparatively higher doses and more frequent administration schedule used in paediatric transplant recipients are the consequence of age-related differences in bioavailability and the possibility of increased metabolic clearance of the drug in younger patients.

MeSH Terms
Adolescent Adult Aging/metabolism Area Under Curve Biological Availability Bone Marrow Transplantation/immunology,physiology Child Child, Preschool Cyclosporine/administration & dosage,pharmacokinetics,therapeutic use Drug Monitoring Heart Transplantation/immunology,physiology Humans Immunosuppressive Agents/administration & dosage,pharmacokinetics,therapeutic use Infant Kidney Transplantation/immunology,physiology Liver Transplantation/immunology,physiology Middle Aged Organ Transplantation/physiology Tissue Distribution
Chemicals
Immunosuppressive Agents Cyclosporine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cooney G F
Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA. cooneygf@vm.temple.edu
Habucky K
Hoppu K
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67 references, click to expand
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Article Info
Journal
Clinical pharmacokinetics
Abbr.
Clin Pharmacokinet
ISSN
0312-5963
DOI
10.2165/00003088-199732060-00004
Email
cooneygf@vm.temple.edu
Published
1997-06-00
Pages
481-95
Language
English
Region
Switzerland
NLM ID
7606849
Subset
IM
External Links
PubMed source DOI: 10.2165/00003088-199732060-00004 View journal details
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