Decreased cyclosporine exposure during the remission of nephrotic syndrome.

In this paper, we report the pharmacokinetics changes observed in seven children with steroid-resistant nephrotic syndrome (SRNS). They received cyclosporine A (CsA) microemulsion 6 mg/kg/day and, one week later, they were admitted to perform a 12-h pharmacokinetic profile with eight time sample points. The pharmacokinetic profile was repeated at 24 weeks of treatment, when all patients achieved remission. Blood concentration against time curves were constructed for each patient at weeks 1 and 24 of CsA treatment. Peak concentrations (C (max)) and the time needed to reach peak concentrations (t (max)) were directly determined from these plots. The area under the curve (AUC) was estimated by the trapezoidal rule. There was a statistically significant difference of the AUC, trough levels, and t (max) between weeks 1 and 24, with a decrease of AUC from 5,211 ng*h/ml in week 1 to 3,289 ng*h/ml in week 24, the trough levels decreased from 157 ng/ml to 96 ng/ml, and the t (max) decreased from 1.85 h to 1.00 h. The higher CsA bioavailability during the nephrotic state has to be considered when managing patients, since the target AUC cannot be the same throughout the treatment.

[Pharmacologic clinical monitoring of serum vancomycin levels in pediatric patients]. / Monitoreo clínico farmacológico de los niveles séricos de vancomicina en pacientes pediátricos.

OBJECTIVE: To analyze the results from the clinical monitoring of serum vancomycin levels among pediatric patients receiving this drug. METHODS: Retrospective study of data from routine monitoring of serum vancomycin concentrations. The study population includes children who received vancomycin for more than 3 days and had peak and trough vancomycin serum concentration documented. The vancomycin concentrations were measured by an immunoassay procedure. RESULTS: We obtained 70 vancomycin concentrations from pediatric patients whose ages ranged from newborn to 13 years old. Mean peak and trough concentrations were 45.7 +/- 8.0 and 18.7 +/- 9.6 micrograms/mL, respectively. We used as a reference normal ranges for Cpmax of 25-40 micrograms/mL and Cpmin of 5-40 micrograms/mL. Only 26.1% of the patients were on Cpmax normal ranges, 47.8% were above the range and 26% under the lower limit. In regards to the Cpmin 17% of the cases were between the accepted limits, 41% above the upper limit and 41% under the normal range. CONCLUSION: Our data suggest that less than a fifth of the patients have serum levels on therapeutic range and almost half of these population had serum levels above the normal range. This might be explained by the type of the population sampled, reflecting a selection bias by detecting levels only among patients with an increased risk for toxicity. Finally, we stress the importance of accurately documenting dose, timing, and renal function in the records of all patients subjected to serum vancomycin determinations.

Efecto de la nutrición y ambiente sobre el metabolismo noradrenérgico en el sistema nervioso central: I. Desnutrición animal / Effect of nutrition and environment on nordrenergic metabolism in the central nervous system: I. animal malnutrition

Se presentan los resultados preliminares de la concentración de noradrenalina (NA) y actividad enzimática de dihidroxi-L-fenil-alanina descarboxilasa (DOPAD 4.1. 1.26) en cuatro regiones encefálicas (corteza, hemisferios sin corteza, tallo y cerebelo) en 32 ratas de la cepa Wistar, distribuidas aleatoriamente en un diseño factorial 2 x 3, con dos niveles de nutrición (bien nutridas y desnutridas) y tres condiciones ambientales (estimulación, control y aislamiento). A los 50 días de vida postnatal fueron sacrificadas, se extrajo el encéfalo y se midieron las concentraciones de NA y actividad de la enzima DOPAD. En la concentración de NA por gramo de tejido seco de las cuatro regiones encefálicas estudiadas, se observaron diferencias estadísticamente significativas entre ratas estimuladas y aisladas. Las ratas estimuladas presentaron altas concentraciones de NA. La actividad de la enzima DOPAD por gramo de tejido seco y por hora se mostró baja en los animales que se mantuvieron con sobreestimulación, difiriendo significativamente de las ratas aisladas. Las pendientes de regresión entre la concentración de NA y actividad de DOPAD, fueron contrastadas mediante análisis de covarianza y se obtuvo que los índices de regresión en ratas estimuladas son mayores que los observadores en los subgrupos aislados. No hubo diferencia en el factor nutricional