Cyclosporin monitoring in Australasia: 2002 update of consensus guidelines

Therapeutic drug monitoring of cyclosporin (CsA) has been established as part of the routine clinical treatment of patients following organ transplantation for more than 20 years, and based on contemporary knowledge, many consensus guidelines have been published to assist clinics and laboratories attain optimal strategies for patient care. This article addresses the newer directions in CsA monitoring, with particular reference to the Australasian situation that has evolved since the 1993 Australasian guideline (1). These changes have included the introduction of alternative assay methodologies, changed CsA formulation from Sandimmun to Neoral throughout Australasia, and alternatives to trough concentration (C0) monitoring, especially 2-hour concentration (C2) monitoring and associated validated dilution protocols to accurately quantitate the higher whole blood CsA concentrations. The revision was prepared following a recent survey of all Australasian CsA-monitoring laboratories (2) where discordant practices were evident.

Sampling times for monitoring tacrolimus in stable adult liver transplant recipients

The aim of this study was to determine the most informative sampling time(s) providing a precise prediction of tacrolimus area under the concentration-time curve (AUC). Fifty-four concentration-time profiles of tacrolimus from 31 adult liver transplant recipients were analyzed. Each profile contained 5 tacrolimus whole-blood concentrations (predose and 1, 2, 4, and 6 or 8 hours postdose), measured using liquid chromatography-tandem mass spectrometry. The concentration at 6 hours was interpolated for each profile, and 54 values of AUC(0-6) were calculated using the trapezoidal rule. The best sampling times were then determined using limited sampling strategies and sensitivity analysis. Linear mixed-effects modeling was performed to estimate regression coefficients of equations incorporating each concentration-time point (C0, C1, C2, C4, interpolated C5, and interpolated C6) as a predictor of AUC(0-6). Predictive performance was evaluated by assessment of the mean error (ME) and root mean square error (RMSE). Limited sampling strategy (LSS) equations with C2, C4, and C5 provided similar results for prediction of AUC(0-6) (R-2 = 0.869, 0.844, and 0.832, respectively). These 3 time points were superior to C0 in the prediction of AUC. The ME was similar for all time points; the RMSE was smallest for C2, C4, and C5. The highest sensitivity index was determined to be 4.9 hours postdose at steady state, suggesting that this time point provides the most information about the AUC(0-12). The results from limited sampling strategies and sensitivity analysis supported the use of a single blood sample at 5 hours postdose as a predictor of both AUC(0-6) and AUC(0-12). A jackknife procedure was used to evaluate the predictive performance of the model, and this demonstrated that collecting a sample at 5 hours after dosing could be considered as the optimal sampling time for predicting AUC(0-6).

On the modelling of wave breaking and set-up on coral reefs

An extended refraction-diffraction equation [Massel, S.R., 1993. Extended refraction-diffraction equation for surface waves. Coastal Eng. 19, 97-126] has been applied to predict wave transformation and breaking as well as wave-induced set-up on two-dimensional reef profiles of various shapes. A free empirical coefficient alpha in a formula for the average rate of energy dissipation [epsilon(b)] = (alpha rho g omega/8 pi)(root gh/C)(H-3/h) in the modified periodic bore model was found to be a function of the dimensionless parameter F-c0 = (g(1.25)H(0)(0.5)T(2.5))/h(r)(1.75), proposed by Gourlay [Gourlayl M.R., 1994. Wave transformation on a coral reef. Coastal Eng. 23, 17-42]. The applicability of the developed model has been demonstrated for reefs of various shapes subjected to various incident wave conditions. Assuming proposed relationships of the coefficient alpha and F-c0, the model provides results on wave height attenuation and set-up elevation which compare well with experimental data. (C) 2000 Elsevier Science B.V. All rights reserved.