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Large between-and within-patient variability has been observed in the pharmacokinetics of mycophenolic acid (MPA). However, conflicting results exist about the influence of patient characteristics that explain the variability in MPA exposure. This population pharmacokinetic meta-analysis of MPA in renal transplant recipients was performed to explore whether race, renal function, albumin level, delayed graft function, diabetes, and co-medication are determinants of total MPA exposure. A total of 13,346 MPA concentration-time data points from 468 renal transplant patients who participated in six clinical studies were combined and analyzed retrospectively. Sampling occasions ranged from day 1 after transplantation to 10 yr after transplantation. Concentration-time data were analyzed with nonlinear mixed-effect modeling. Exposure to total MPA, as determined by MPA clearance, significantly increased with increasing renal function, albumin level, and hemoglobin as well as decreasing cyclosporine predose level (P < 0.001). These variables could explain 18% of the between-patient and 38% of the within-patient variability in MPA exposure. Differences in MPA exposure between patients with or without delayed graft function or between patients of different races are likely to be caused by the effect of renal function on MPA exposure. Diabetes did not have an effect on MPA exposure. The clinical implication is that a change in renal function or albumin level provides an indication for therapeutic drug monitoring as MPA exposure may be altered. Patients in whom cyclosporine and mycophenolate mofetil are combined may need higher mycophenolate mofetil doses, especially during the early phase after transplantation than currently recommended for optimal MPA exposure.

The cognitive-behavioral model of stress and coping provided the framework for this study of mothers of physically disabled children (n = 69) and mothers of nondisabled children (n = 63). The first aim was to test for differences between groups in responses to stressful parenting events. As hypothesized, mothers of disabled children reported higher levels of depressive symptomatology. Differences in psychological distress and health status approached significance. The second aim was to explore the mediating influences of coping strategies and cognitive appraisals. As predicted, emotion-focused coping was related to increased psychological distress in mothers of disabled children whereas problem-focused coping was associated with decreased distress. Both relationships were significant even after controlling for differences in type of parenting stressor. Hierarchical regressions showed that 58 and 25% of the variance in psychological distress was explained by the independent variables; however, the predictors were different for the two groups of mothers. Factors that may explain the differential effectiveness of coping and appraisal, and clinical implications of this study are discussed.