CYCLOSPORINE PHARMACOKINETICS IN PEDIATRIC TRANSPLANT RECIPIENTS

Cyclosporin is an essential component of the antirejection drug protoc ol used in the long term management of paediatric organ transplant rec ipients. 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 a dult transplant recipients. There are limited data on the pharmacokine tics of cyclosporin in paediatric transplant recipients (14 publicatio ns provide the database) as compared with the adult transplant populat ion. Study design, analytical methodology and age ranges of the indivi duals differ between studies, making comparative interpretation of pha rmacokinetic data difficult. However, significant trends are noteworth y and these may influence dose administration guidelines and therapeut ic monitoring standards for cyclosporin in the paediatric organ transp lant recipient. The bioavailability of the oral formulations of cyclos porin is highly variable as with the adult population, but there appea rs to be a correlation between cyclosporin bioavailability and age wit h both the traditional oral formulation (Sandimmun(R)) and the new mic roemulsion formulation (Neoral(R)) in young liver transplant patients. Bowel length, presystemic metabolism in the gut wall, type of transpl ant and time since transplant are contributing factors in the variatio n of bioavailability patterns in paediatric transplant patients. The v olume of distribution of cyclosporin does nut appear to differ between paediatric and adult transplant recipients, but systemic clearance is comparatively higher in the paediatric population. In general, paedia tric patients require higher doses of cyclosporin to achieve target bl ood 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 sc hedule 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 tr ansplant recipients are the consequence of age-related differences in bioavailability and the possibility of increased metabolic clearance o f the drug in younger patients.