Search

Objectives: The aim of this study was to develop a limited sampling strategy (LSS) for monitoring the use of mycophenolic acid (MPA) in maintenance therapy with tacrolimus (TCL) in renal transplant patients. Methods: Eighteen adult patients receiving a first transplant were investigated. All patients were treated with a combination of TCL, steroid and mycophenolate mofetil (MMF). Besides the predose trough concentration ( C0), whole blood samples were taken for measurement of the MPA concentration at 0·5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 h for a 14-point 12-h pharmacokinetic (PK) profile. Using stepwise linear regression analysis, an abbreviated area under the concentration time curve (AUC) was calculated using all 14, and any combination of sampling points to give an estimating equation with up to three predictors. Results: The equation derived from C2, C7 and C12, for AUC estimation: AUC = (2·05 × C2) + (8·51 × C7) + (2·29 × C12) + 4·24. was found to be optimal. Using this formula, there was an excellent correlation between the estimated 3-point AUC and AUC0–12 h. To assess the agreement between the abbreviated methods and the full PK profile, we plotted the average AUC of the abbreviated estimates and the full PK profile. This Bland-Altman analysis indicated good agreement to within ±2 SD and a prediction variability of 7·56 μg × h/mL. Conclusion: Our proposed three-sampling-point estimate of AUCs is clinically acceptable. However, the sampling times are inconvenient for outpatients, and is recommended only for monitoring MMF treatment of inpatients with suspected toxicity or at high risk of organ rejection. [ABSTRACT FROM AUTHOR]

A column-switching high-performance liquid chromatographic analysis was established to monitor the serum concentration of mycophenolic acid, the active metabolite from mycophenolate mofetil administered for the prophylaxis of acute organ rejection in renal transplantation. The system consisted of two pumps for solvent delivery, a column-switching valve, a precolumn, and a reversed-phase analytical column. The present method enabled us to determine MPA by injecting serum samples directly into HPLC without any pretreatment. The mobile phases with different amounts of organic solvent were delivered to the precolumn and analytical column by separate lines, and samples were applied to the precolumn. The column switching valves were switched automatically following the processes for the elimination of protein and the drug analysis. The peak heights of MPA were linearly related to the concentrations (r=0.999) in the range of 0.1–20 μg/ml, and the limit of quantification was 0.1 μg/ml (S/N ratio=3). This method was accurate and reproducible on the basis of the results of recovery (94.0–98.0%) and small coefficient of variations of intra and inter-assay (less than 8.3%). [ABSTRACT FROM AUTHOR]