Changes of Respiratory Exchange Ratio in Children and Adolescents: A Longitudinal Study.

We conducted a longitudinal study to examine changes in the respiratory exchange ratio (RER) during progressively increasing body exertion in children and adolescents of female sex. In this analysis we only included 23 examinees for which we had all yearly measurements from examinee's age 9 years until 18 years of age. The data were analyzed according to the chronological and biological age. According to both criteria, the highest RER values were recorded at moments of maximum exertion and they did not increase with age. We found the highest RER values were in the year of the menarche. We interpret these results as related to the effect of estrogen. The beginning of sexual development involves a gradual increase in estrogen plasma concentrations. At one point serum levels of estrogen reach a level high, enough to allow for maximum RER values, i.e. causing the optimum anaerobic capacity of the examinee. This threshold estrogen value varies between individuals.

Effect of cyclosporine on steady-state pharmacokinetics of MPA in renal transplant recipients is not affected by the MPA formulation: analysis based on therapeutic drug monitoring data.

BACKGROUND: Two oral mycophenolic acid (MPA) formulations, immediate-release mycophenolate mofetil and enteric-coated mycophenolate sodium, have been shown to differ regarding some drug-drug interactions. The aim was to assess whether the effects of cyclosporine (CsA) on steady-state pharmacokinetics (PK) of MPA in renal transplant patients were affected by MPA formulation. METHODS: A prospective, stratified observational study based on therapeutic drug monitoring of MPA (6 total plasma concentrations over a 12-hour dosing interval, τ) in consecutive stable adult renal transplant recipients (n = 68). RESULTS: Patients treated with enteric-coated mycophenolate sodium (n = 45) or mycophenolate mofetil (n = 23) and with either CsA (microemulsion, n = 43) or tacrolimus (Tac) (immediate release, n = 25) were comparable regarding demographics, comorbidity, renal and liver functions, comedication, corticosteroid dose, CsA or Tac dose, and trough concentrations. Based on dose-normalized MPA concentrations and with adjustment for age, sex, body mass index, estimated glomerular filtration rate, and corticosteroid dose, CsA (as compared with Tac) consistently reduced MPA area under the concentration-time curve during the dosing interval at steady state overall [geometric mean ratio (GMR), 0.78; 95% confidence interval, 0.62-0.99] and by MPA formulation (by 22% and 21%, respectively), increased CLT/F,ss overall (1.31; 1.00-1.70) and by formulation (by 25% and 36%, respectively), reduced morning predose MPA concentration overall (0.59; 0.38-0.92) and by formulation (by 34% and 47%, respectively), increased peak-trough fluctuation overall (1.51; 1.06-2.17) and by formulation (by 58% and 45%, respectively), and prolonged tmax,ss overall (adjusted median difference 0.58, 0.04-1.12 hours) and by formulation (by 0.6 and 0.5 hours, respectively). CONCLUSIONS: Qualitatively and quantitatively, the effect of CsA on steady-state PK of MPA is not conditional on MPA formulation.