No abstract

Predose plasma mycophenolic acid (MPA) concentrations measured with a semi-automated enzyme-multiplied immunoassay were related to adverse events (e.g., rejection, leukopenia, infection), drug dose, and clinical status in 147 adult and 63 pediatric liver allograft recipients receiving adjunctive immunosuppression with mycophenolate mofetil (MMF). In 12 of 13 acute rejection episodes, predose MPA levels were below the 1 mg/L cut-off defined using receiver operating characteristic (ROC) curve analysis. The relative risk of developing infection or leukopenia increased more than 3-fold above predose MPA levels of 3 to 4 mg/L. Plasma MPA levels correlated weakly (r 2 ‫؍‬ 0.081) with MMF dose and the dose / level relationship was variably influenced by age, the indication for MMF, concentrations of serum albumin and creatinine, and comedication with tacrolimus or cyclosporine. The median mycophenolate dose required per unit mycophenolate level was 50% lower in children than in adults. Comparable drug requirements were also decreased by renal dysfunction (by 40 and 43% in adults and children, respectively), and in patients prescribed MMF alone rather than with tacrolimus or cyclosporine. However, in patients with serum albumin less than 35g/L, MMF dose requirements were higher than in those with normal albumin levels (by 2.1-and 2.6-fold in adults and children, respectively). In adults, 44.7% achieved clinically acceptable therapeutic MPA concentrations at a dose less than 1 g MMF twice daily and only 6.3% required 1.5 g twice daily as suggested by the manufacturer. The immunoassay was a rapid, reliable, and acceptably precise technique in which only 10.8% of measurements were unproductive. In conclusion, our data suggests that MPA predose level monitoring is both clinically-and cost-effective and that a therapeutic range of 1 to 3.5mg/L (by immunoassay) is applicable in liver allograft recipients given adjunctive MMF. (Liver Transpl 2004;10:492-502.)

Our results do not suggest that increased central 5-HT function is a trait marker in anorexia nervosa, but dysregulation in part of the central 5-HT system may be a vulnerability factor. The flattened post-meal response to cortisol in the subjects who had recovered from anorexia nervosa suggests that their hypothalamic pituitary--adrenal axis may be altered and deserves further investigation.

Determinants of the wide interindividual variability of the pharmacokinetics of mycophenolic acid (MPA) in 21 stable pediatric liver transplant recipients were investigated in relation to the kinetics of the drug's major phenolic glucuronide metabolite (MPAG), cyclosporin (CsA), or tacrolimus (Tac) co-medication and liver and renal function. Trough concentrations (C(0) ) most reliably predicted the area under the curve (AUC) of 0-7 hours MPA plasma concentrations (r (2) = 0.650). Co-medication with CsA demanded higher MPA mofetil (MMF) doses to achieve equivalent trough levels than Tac (362 vs. 178 mg per mg/L, P= 0.004). Median MPA C(0) (range) was significantly lower during CsA co-therapy when corrected for MMF dose (2.8 vs. 5.6 mg MPA/L for Tac, P= 0.006). The AUC of MPAG was correspondingly higher during CsA co-medication (229 vs. 94 mg/L/h for Tac, P = 0.012) with the MPA-to-MPAG ratio at C(0) correspondingly lower (0.10 vs. 0.14, respectively, P = 0.04). This suggested contrasting effects of CsA and Tac on MPA glucuronidation or its excretion and enterohepatic recirculation. MPAG AUC was correlated to body weight and creatinine clearance. Children with elevated aspartate transaminase (AST; but with no evidence of rejection on liver biopsy, n = 7) had significantly lower MPA trough levels compared with those in whom AST was normal (0. 77 vs. 1.76 mg/L, P = 0.05), but there was no difference in the MMF dose per body weight. Examination of the MPA profiles in these subjects showed significantly lower MPA concentrations from 120 minutes after dose until the end of the 7-hour profile and suggest an accelerated clearance or decreased enterohepatic recirculation.)

Objective Osteopenia is a known complication of anorexia nervosa. Most studies have focused on the features of the illness which predict bone complications. The few reports on recovery have been conflicting, with some studies suggesting restoration of normal bone mass with recovery from anorexia nervosa, while others suggest that the improvement may only be partial. This is the first report of bone density in a long‐term recovered group. Method: We measured bone density in the hip and lumbar spine in 18 recovered women, using dual energy X‐ray absorptiometry. Results: We found an unexpectedly high incidence of osteopenia, with 14 of 18 women affected. Duration of amenorrhea was the best predictor of reduced bone density. An index of the duration of recovery, relating it to the duration of illness, was also highly correlated with outcome. Discussion: Our findings have implications, both for the individual and for the economic burden to society. We suggest that the use of oral contraceptives in women recovering from anorexia nervosa needs further investigation. Additional longitudinal studies are clearly warranted. © 1997 by John Wiley & Sons, Inc. Int J Eat Disord 22: 71–75, 1997.