The impact of omeprazole on mycophenolate pharmacokinetics in kidney transplant recipients

Background@#The absorption rates of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) may be influenced by the concomitant use of omeprazole. @*Methods@#One hundred kidney transplant patients were recruited during their outpatient visits, including 50 on MMF and 50 on EC-MPS. At the clinic, a predose mycophenolic acid (MPA) sample (C0) was collected; subsequently, the participants received the proton-pump inhibitor omeprazole along with either MMF or EC-MPS. Two more blood samples were collected at 1.5 and 3.5 hours and used to estimate an area under the curve (AUC) from zero to 12 hours [AUC (0-12)]. @*Results@#The mean number of months after transplant was 92 months. The median AUC (0-12) and C0 results were 62.2 mg·h/L and 2.0 mg/L for the MMF group and 71.9 mg·h/L and 1.8 mg/L for the EC-MPS group (P = 0.160 and 0.225, respectively). Interestingly, 54% of the MMF group and 62% of the EC-MPS group showed AUCs above the target values. The correlation between MPA C0 and the predicted AUC was poor in both groups. @*Conclusion@#Omeprazole can be safely co-administered with either MMF or EC-MPS, as it did not compromise the MPA exposure. Unexpectedly, however, a high percentage of patients presented MPA AUCs exceeding the target value, highlighting the importance of periodically assessing MPA level.

The impact of omeprazole on mycophenolate pharmacokinetics in kidney transplant recipients

Background@#The absorption rates of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) may be influenced by the concomitant use of omeprazole. @*Methods@#One hundred kidney transplant patients were recruited during their outpatient visits, including 50 on MMF and 50 on EC-MPS. At the clinic, a predose mycophenolic acid (MPA) sample (C0) was collected; subsequently, the participants received the proton-pump inhibitor omeprazole along with either MMF or EC-MPS. Two more blood samples were collected at 1.5 and 3.5 hours and used to estimate an area under the curve (AUC) from zero to 12 hours [AUC (0-12)]. @*Results@#The mean number of months after transplant was 92 months. The median AUC (0-12) and C0 results were 62.2 mg·h/L and 2.0 mg/L for the MMF group and 71.9 mg·h/L and 1.8 mg/L for the EC-MPS group (P = 0.160 and 0.225, respectively). Interestingly, 54% of the MMF group and 62% of the EC-MPS group showed AUCs above the target values. The correlation between MPA C0 and the predicted AUC was poor in both groups. @*Conclusion@#Omeprazole can be safely co-administered with either MMF or EC-MPS, as it did not compromise the MPA exposure. Unexpectedly, however, a high percentage of patients presented MPA AUCs exceeding the target value, highlighting the importance of periodically assessing MPA level.

Serum COMP and their correlations with various disease parameters in patients with systemic lupus erythematosus and osteoarthritis

The cartilage oligomeric matrix protein [COMP] is a glycoprotein, which occurs mainly in an articular cartilage. The amount of this protein increases under the influence of cytokines and growth factors. As a result of various diseases that cause damage to cartilage, fragments of matrix protein are released into synovial fluid and then into blood. The assessment of matrix protein level in serum, for example COMP, permits the establishment of the degree of cartilage damage in inflammatory joint diseases, and permits observation of the effectiveness of the treatment. To assess serum COMP level, as a marker for cartilage degradation, in SLE and OA patients and to find a correlation between serum COMP level and other markers as well as activity of disease, disease duration and the age of the patients. Blood was collected from 40 systemic lupus erythematosus [SLE] patients group I, [the patients were further subdivided into two subgroups, group [Ia] comprised 20 SLE patients received 1 g IV methylprednisolone [MP] daily for three successive days, group [Ib] comprised 20 SLE patients did not receive IV methylprednisolone [MP]], and from 20 patients with knee osteoarthritis [OA] group II who constituted the control group. Serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay [ELISA]. The measured values of the serum COMP level in SLE patients ranged from 1.32 to 1.71 microg/ml with a mean of 1.51 +/- 0.13 microg/ml in group [Ia], and ranged from 2.43 to 3.56 microg/ml with a mean of 2.86 +/- 0.31 microg/ml in group [Ib]. While in OA group [II] the value of serum COMP ranged from 0.97 to 2.65 microg/ml with a mean of 1.25 +/- 0.37 microg/ml. We found significantly elevated COMP levels in the SLE group [Ib] compared to the SLE group [Ia] patients and OA group [II] [p < 0.001]. We found a statistically significant positive correlations with the number of tender joints [correlation coefficient Pearson's: r = 0.45, p < 0.01], the number of swollen joints [r = 0.55, p < 0.001], SLAM value [r = 0.56, p < 0.001]. A significant positive correlation was found between serum COMP level and the ESR value in the first hour [r = 0.35, p < 0.001]. While the serum COMP level was independent of the patients' age [r = 0.04, p = NS], disease duration [r = -0.03, p = NS] and morning stiffness duration [r = -0.05, p = NS]. Also a Negative correlation was found between the serum COMP level and haemoglobin value [r = -0.11, p = NS]. As regards the OA group, no correlation was found between the serum COMP level and patients' age [r = -0.05, p = NS] and disease duration [r = 0.24, p = NS]. There were positive correlations between serum COMP and WOMAC index score for the lower limbs [r = 0.64, p < 0.05]. The serum COMP level can be an important marker of disease activity and cartilage destruction in SLE and OA Patients, and that serum levels of COMP can be used as a parameter for monitoring the therapy response in SLE patients undergoing an intravenous bolus steroid therapy

Serum BAFF level and its correlations with various disease parameters in patients with systemic sclerosis and systemic lupus erythematosus

Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell-activating factor of the TNF ligand family [BAFF] is essential in their physiology. The role of BAFF, a new cytokine, in autoimmune diseases has been highlighted. To assess serum BAFF level in systemic sclerosis [SSc] and systemic lupus erythematosus [SLE] to verify its role in these diseases and find any relation with the clinical manifestations, laboratory investigations, disease activity and damage. The study included 12 SSc and 40 SLE patients. The patients were subjected to full history taking and thorough clinical rheumatological and dermatological examinations and relevant investigations including autoantibodies and CT chest in SSc. In SSc, the total skin thickness score was scored according to the modified Rodnan skin score [MRSS] method. In SLE, the disease activity was assessed using the Systemic Lupus Activity Measure [SLAM] and organ damage using the Systemic Lupus International Collaborating Clinics/ACR [SLICC/ACR] index. The serum BAFF levels were measured using a specific ELISA. The BAFF level was remarkably elevated in SSc and SLE in a comparable percentage of patients, yet the level was highest in SLE and lower in the limited SSc subtype. The BAFF significantly correlated with the level with the MRSS in SSc and with both the SLAM and SLICC in SLE patients. The elevated level of BAFF in SSc further confirms the importance for new therapeutic targets for its inhibition to slow the disease progression, particularly skin fibrosis. The role of BAFF in the pathogenesis and disease activity in SLE is well-known and the novel noticeable correlation with the damage index high lightens on the utility of BAFF as an indicator of disease damage and predictor of poor outcome