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.

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Five days of Cr supplementation increased body weight and fat-free body mass in resistance-trained men who were classified as responders. Peak force and total force during a repeated maximal isometric bench-press test were also significantly greater in the responders compared to the placebo group.

Administration of antibiotics by the inhalational route has become part of standard protocols for treatment of and prophylaxis for Pseudomonal pneumonias in patients with cystic fibrosis. For tobramycin, however, limited data are available on the aerosol absorption patterns, and no absolute bioavailability data for tobramycin exist. The purpose of this study was to measure the absolute bioavailability and systemic absorption characteristics of tobramycin when administered in high doses by a nebulizer. Multiple serum concentrations of tobramycin were measured after administration of an intravenous dose (mean, 2.9 mg/kg every 6 hours) and after an inhalational dose (5.6 mg/kg over 1 hour). Inhalational doses were superimposed over the "tail" of a steady-state intravenous dose to improve the sensitivity of the assay procedure (Abbott-TDX). Absolute bioavailability (F) was determined from AUC ratios normalized for dose. Model-independent pharmacokinetic parameters (volume of distribution [Vss] and total clearance [CLt]) were determined for each subject. Absorption characteristics (absorption rate constant [Ka] and mean absorption time [MAT]) were assessed after calculation of the cumulative fraction of drug absorbed, amount of bioavailable drug, and percent remaining to be absorbed per unit time using the Loo-Riegelman method. Three men and three women completed the study, and all received concurrent doses of ceftazidime. Mean absolute bioavailability (+/- standard deviation) was 9.13% (+/- 3.82), and the rate of absorption into the systemic circulation was consistent with a zero-order model profile for all subjects. Mean absorption time values reflected a wide degree of subject variability and ranged from approximately 15 to 150 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

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