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Pharmacogenomic (PGx) information is increasingly being incorporated into US Food and Drug Administration-approved drug labels. We reviewed the data source (adults vs. pediatrics) of PGx information in approved drug labels and assessed the suitability of applying adult-derived PGx information and related prescribing recommendations to the care of pediatric patients. We identified 65 drugs with labels containing PGx information and that have also been evaluated in children and found that in the majority of cases (56/65, 86%), the PGx information described was derived from adult studies. The application of PGx information from adults to pediatrics was deemed suitable for 71.4% ( n = 40) of the drugs and unclear for 28.6% ( n = 16). An ontogeny effect, limited or conflicting data regarding ontogeny of the genetic biomarker, or a difference in the pathophysiology or progression of the adult vs. pediatric disease were the primary reasons for deeming direct application from adults to pediatrics unclear. [ABSTRACT FROM AUTHOR]

Background: Tumor enlargement after chemotherapy is considered one of the high-risk factors for local recurrence and survival in osteosarcoma. We hypothesized patients with this risk factor will have similar survival regardless of the development of local recurrence.Questions/purposes: We asked (1) the prognostic factors for survival in our cohort, (2) how much effect local recurrence has on survival among patients with similar preoperative risk factors, and (3) what prognostic factors are important for survival in these selected patients.Methods: We analyzed the prognostic factors for survival in 449 patients with extremity osteosarcoma without metastatic disease at initial diagnosis and treatment (38 with local recurrence, 411 without local recurrence). We compared the survival difference between patients with local recurrence (n = 38) and without local recurrence (control, n = 76) matched for age, location, initial tumor volume, and tumor volume change after chemotherapy, and assessed prognostic factors in this subgroup.Results: In a cohort study, multivariate analysis revealed initial tumor volume, tumor enlargement, inadequate margin, and local recurrence predicted poor survival. In the case-control study, the 10-year metastasis-free survival rates of two groups were 13.1 ± 10.7% and 19.3 ± 9%, respectively. In the case-controlled groups, tumor enlargement and initial tumor volume showed multivariate significance.Conclusions: Local recurrence has a small impact on survival in patients with high-risk osteosarcoma.Level Of Evidence: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

A prospective cohort study was performed to determine the optimal dose of vancomycin to maintain a serum trough concentration of at least 15 to 20 mg/l and to assess the efficacy of this target vancomycin concentration in the treatment of methicillin-resistant Staphylococcus aureus pneumonia. Vancomycin pharmacokinetic parameters were estimated using a CAPSIL software program from serum concentrations of 141 patients with pneumonia treated with vancomycin, regardless of methicillin-resistant Staphylococcus aureus status, at a 28-bed medical intensive care unit. Vancomycin trough concentrations and other pharmacokinetic parameters were compared between five groups of patients differing in their renal function: (1) creatinine clearance > or =60 ml/minute, (2) creatinine clearance 30 to 60 ml/minute, (3) creatinine clearance <30 ml/minute, (4) on intermittent haemodialysis, and (5) on continuous renal replacement therapy. More than 70% of patients failed to reach the recommended therapeutic serum trough concentrations: a higher dose of vancomycin is necessary to maintain serum trough concentration at 15 to 20 mg/l, particularly in critically ill patients with creatinine clearance above 60 ml/minute and in those on intermittent haemodialysis. Among patients with methicillin-resistant Staphylococcus aureus pneumonia, no significant differences were observed in the treatment success rate, length of intensive care unit stay, and intensive care unit mortality rate between patients with vancomycin trough concentrations of >20 mg/l, 15 to 20 mg/l and <15 mg/l. [ABSTRACT FROM AUTHOR]

The purpose of this study was to characterize the pharmacokinetic parameters of mycophenolic acid (MPA) in Korean kidney transplant recipients. Plasma MPA concentrations of 10 Korean kidney transplant recipients administered a lower dose of mycophenolate mofetil (MMF; 750 mg twice a day) were measured at 2 weeks of MMF therapy by high-performance liquid chromatography (HPLC). The plasma MPA concentration-time curve pattern of patients taking lower doses of MPA was consistent with previously reported profiles of patients taking the fully recommended doses. The plasma MPA concentration-time curve was characterized by an early sharp peak within 1 hour and a small second peak in some patients at 4 to 12 hours postdose. The mean C(max) and AUC were 8.73 +/- 4.65 microg/mL and 18.45 +/- 4.25 microg*h/mL, respectively. The mean fraction of free MPA was 1.60% +/- 0.23%. Patients' age, weight, body surface area, and renal function did not influence the AUC. The free fraction of MPA appeared not to be affected by serum albumin and renal function when creatinine clearance was above 40 mL/min. Regression analysis between each plasma concentration and AUC for the limited sampling strategy of MMF therapeutic drug monitoring demonstrated that the concentrations of predose and 1- and 8-hour postdose were positively correlated with AUC (r = 0.74545, p = 0.0133; r = 0.68485, p = 0.0289; and r = 0.63636, p = 0.0479, respectively). The pattern of the concentration-time profile of MPA in Korean kidney recipients was similar to the results of other studies performed in Caucasians, although there was interindividual variability of AUC, C(max), and t(max). MPA concentrations of predose and 1- and 8-hour postdose were positively correlated with AUC. [ABSTRACT FROM AUTHOR]

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events. [ABSTRACT FROM AUTHOR]