Therapeutic monitoring of mycophenolic acid in renal transplanted patients by a validated HPLC method.

INTRODUCTION: Mycophenolate mofetil and its active metabolite mycophenolic acid are routinely used as immunosuppressant drugs in solid organ transplantation in a fixed daily dose regimen in association with cyclosporine, tacrolimus and steroids. Therapeutic drug monitoring for mycophenolic acid concentration has been suggested to optimize outcomes by reducing rejection and drug related toxicities in clinical renal transplantation. AIM: To determine the predose concentration of mycophenolic acid in renal transplanted patients by a validated proposed high-performance liquid chromatography (HPLC) method and to estimate the interindividual variability based on the therapeutic target. MATERIALS AND METHODS: An HPLC method combined with protein precipitation has been validated for mycophenolic acid determination in the human plasma obtained from 21 renal transplant recipients. HPLC analysis was carried out using the chromatographic system Agilent Technologies 1200 DAD. Samples were injected manually, and the compounds were separated on a LiChrosphere® select B C18 analytical column. The mobile phase was 45:55 (v/v) acetonitrile-buffer phosphate, pH 2.5, flow rate of 1.0 mL/min and column temperature of 30°C. Detection was performed at 215 nm. Whole blood samples were collected into vacutainers containing EDTA and separated at 6000 g for 10 minutes. A 200-µL aliquot of patient plasma was transferred to a tube, followed by addition of 10 µL of naproxen as internal standard and 400 µL of acetonitrile (v/v) as a protein precipitating agent. Each tube was vortex-mixed for 30 sec and then centrifuged for 10 min at 10000 rpm. 20 µL of the supernatant was injected into the HPLC system for analysis. RESULTS: The method showed appropriate linearity for MPA with correlation coefficient greater than 0.999. High inter-patient variability is observed with 18% of patients within the target trough concentration range, 27% of patients below the target trough concentration range and 54% over the range with risk of toxicity. CONCLUSIONS: Therapeutic monitoring of MPA might contribute to a better management of renal transplant recipient with the goal of optimizing therapeutic regimens in order to reduce the risk of rejection and MPA-related toxicity.

Vitamin D and Its Role as a Protective Factor in Allergy.

The relationship between vitamin D status and asthma has been subject to several studies in the last decade. Epidemiological data suggest that incidence of asthma and atopic diseases increased significantly in most Westernized countries. The significant variation between countries suggests that besides genetic factors, environmental aspects play a role in the pathogenesis of atopy. The prevalence of hypovitaminosis D is high in many industrialized countries. In addition to its relationship with bone metabolism, vitamin D is recognized as an immunomodulator, with important effects on both adaptive and innate immunity. Correlations between vitamin D status and asthma have been formulated, with a considerable interest in assessing whether this vitamin protects against or reduces asthma morbidity. In this review, we discuss recent findings regarding vitamin D status throughout Europe and its influence over asthma and allergic rhinitis prevalence. Geographical latitude and dietary habits may explain the lower prevalence of allergic disease in Albania. We also consider the effects of vitamin D supplementation in allergic disease. Several clinical trials are under way and their results are needed in order to make definitive recommendations about the optimal dose of vitamin D for prevention and treatment of asthma and allergic disease.