ABSTRACT
BACKGROUND: Levothyroxine by IV administration is often prescribed in the intensive care unit for the management of potential solid organ donors, following declaration of brain death and provision of consent for organ donation. Published data on the stability of levothyroxine in IV solutions are limited. OBJECTIVE: To evaluate the physical compatibility and chemical stability, over a 24-h period, of 2 concentrations of levothyroxine in 0.9% sodium chloride with storage at room temperature and with exposure to or protection from light. METHODS: Levothyroxine solutions (0.4 µg/mL and 2.0 µg/mL) were prepared in 50-mL minibags of 0.9% NaCl and stored at room temperature (25°C) with exposure to or protection from light. Samples were collected from each minibag at time 0 and after 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, 12.0, and 24.0 h. The samples were analyzed in triplicate with a validated stability-indicating high-performance liquid chromatography method using ultraviolet detection. A solution was considered stable if it maintained 90% of its initial concentration of levothyroxine. Changes in colour, clarity, and pH were assessed to determine the physical compatibility of the solutions. RESULTS: All samples remained clear, colourless, and free of precipitate throughout the study, and there were no significant changes in pH. Based on the 95% confidence interval of the slope of the curve relating concentration to time determined by linear regression, solutions of levothyroxine with concentration 0.4 µg/mL would maintain at least 90% of the initial concentration for 16.9 h with exposure to light and for 18.0 h if kept in the dark. Solutions of levothyroxine with concentration 2.0 µg/mL would maintain at least 90% of the initial concentration for 6.5 h with exposure to light and for 12.0 h if kept in the dark, with 95% confidence. CONCLUSIONS: Extemporaneously prepared solutions of levothyroxine in 0.9% NaCl can be expected to remain stable for at least 6.5 h if stored without protection from light and at least 12 h if stored in the dark. Stability is related to concentration, with more dilute solutions having greater stability.
ABSTRACT
Cyclosporine (CSA; Neoral) is one of the most common immunosuppressants used in pediatric renal transplantation. Research in adult renal transplant recipients has shown that 2-h post-dose concentration (C2) monitoring and limited sampling strategies (LSSs) are better at predicting drug exposure and outcome than trough concentrations (C0). While C0 monitoring is the usual practice in pediatric renal transplant patients, area under the curve (AUC) monitoring has been shown to be superior in terms of predictive ability and outcomes. However, AUC monitoring is impractical and inconvenient in a clinic setting because it involves many blood samples. An LSS provides a reliable alternative. The purpose of this study was to prospectively define an LSS (AUC(0-12)) for CSA monitoring and to test its predictive performance. As well, an LSS (AUC(0-4)) for CSA was developed and its predictive performance tested. Blood samples for CSA concentrations were collected in 29 stable pediatric renal transplant patients prior to (t = 0) and at 0.5, 1, 2, 4, 6, and 8 h following a steady-state morning CSA dose. AUC was calculated by the trapezoidal method; LSSs for AUC(0-12) and AUC(0-4) were determined using multiple regression analysis in 14 patients; and the LSSs' predictive performance was tested in 15 additional patients. Both LSSs require two blood samples. For the LSS (AUC(0-12)), blood samples are required immediately before the dose and 2 h post-dose: AUC(0-12) = 12.45 C0 + 2.17 C2 + 723.16 (r2 = 0.909). For the LSS (AUC(0-4)), blood samples are required at one and 2 h post-dose, AUC(0-4) = 1.17 C1 + 1.85 C2 - 41.00 (r2 = 0.971). The LSSs demonstrated low bias and high precision for both AUC(0-12) and AUC(0-4). Our two-concentration LSSs are accurate and precise predictors that are more clinically useful for our patient population than other LSSs that have been developed for pediatric renal transplant patients. Our study template provides a guide for other centers to develop accurate and precise LSSs specific to their own patient population.
