ABSTRACT
Objetivo: Validar un modelo para la monitorización farmacocinética de los tratamientos con vancomicina intraperitoneal en pacientes sometidos a diálisis peritoneal continua ambulatoria con peritonitis bacteriana. Método Se realiza un estudio prospectivo, abierto, en 2 cohortes: la primera incluye a 10 pacientes de 56±14 años y 65±5kg y la segunda, otros 10 pacientes (12 episodios de peritonitis) de 52±13 años y 64±8kg. El tratamiento consiste en la instilación y retención durante 6h en la cavidad peritoneal de una solución conteniendo 2g de vancomicina y 1g de ceftazidima, en 2 l de dializante. Tras la instilación del antibiótico, se obtuvieron muestras de sangre a las 4, 6, 8, 10, 24, 48 y 168h, en la primera cohorte y a las 6 y 120h (CVAN120) en la segunda. El modelo farmacocinético se desarrolla a partir de los parámetros obtenidos en la primera cohorte y se valida en la segunda cohorte calculando el error medio (EM) y el error cuadrático medio de predicción (ECM) de la CVAN120.ResultadosLas concentraciones séricas de vancomicina decaen desde 39,63±7,62 mcg/ml a las 4h, hasta 8,55±2,87 mcg/ml a las 168h, en la primera cohorte, y desde 37,65±6,84 mcg/ml a las 6h, hasta 10,82±2,66 mcg/ml a las 120h (CVAN120), en la segunda. Los parámetros farmacocinéticos fueron: Cl=0,006 l/h/kg y Vd:=0,52 l/kg en la primera cohorte, y Cl=0,006 l/h/kg y Vd:=0,53 l/kg, en la segunda. El EM y el ECM de predicción de la CVAN120 fueron, respectivamente, 0,59 mcg/ml ([EM*100/CVAN120]=5,5%) y 10,38 mcg2/ml2 ([ECM*100/(CVAN120)2]=8,9%).Conclusión El modelo presentado muestra una exactitud y precisión adecuadas para la monitorización de la vancomicina intraperitoneal en pacientes sometidos a diálisis peritoneal continua ambulatoria con peritonitis bacteriana (AU)
Objective: To validate a pharmacokinetic model of the treatments with intraperitoneal vancomycin applied to patients on continuous ambulatory peritoneal dialysis with bacterial peritonitis. Methods: To carry out a prospective study divided in 2 cohorts: the first one including ten patients of 56 ± 14 years and 65 ± 5 kg, and the second one with 10 patients (12 episodes of peritonitis) aged 52 ± 13 years and 64 ± 8 kg. The treatment consists of administering and retaining for 6 h in the peritoneal cavity a solution containing 2 g of vancomycin and 1 g of ceftazidime into 2 l of dialysis solution. After the antibiotic administration, blood samples were obtained at 4, 6, 8, 10, 24, 48 and 168 h in the first cohort and at 6 and 120 h (CVAN120) in the second. The pharmacokinetic model was developed from the parameters obtained from the first cohort and was validated by the second cohort, calculating the mean error (ME) and the mean squared prediction error (MSPE) of the CVAN120.Results: Vancomycin serum concentrations fell from 39.63 ± 7.62 mcg/ml at 4 h to 8.55 ± 2.87mcg/ml at 168 h for the first cohort, and from 37.65 ± 6.84 mcg/ml at 6 h to 10.82 ± 2.66 mcg/mlat 120 h (CVAN120) for the second cohort. The pharmacokinetics parameters were: C1 = 0.0061/h/kg and Vd: = 0.52 1/kg for the first cohort, and C1 = 0.006 1/h/kg and Vd: = 0.53 1/kg for the second. The predictive ME and MSPE of the CVAN120. were 0.59 mcg/ml ([EM*100/CVAN120 = 5.5%)and 10.38 mcg2/ml2([MES*100/(CVAN120)2]) respectively. Conclusion: The presented model shows an adequate exactitude and precision for the monitoring of intraperitoneal vancomyc in in patients submitted to continuous ambulatory peritoneal dialysis with peritonitis (AU)
Subject(s)
Humans , Drug Monitoring/methods , Peritoneal Dialysis/methods , Dialysis Solutions/pharmacology , Vancomycin/administration & dosage , Peritonitis/drug therapy , Renal Insufficiency, Chronic/therapyABSTRACT
OBJECTIVE: To validate a pharmacokinetic model of the treatments with intraperitoneal vancomycin applied to patients on continuous ambulatory peritoneal dialysis with bacterial peritonitis. METHODS: To carry out a prospective study divided in 2 cohorts: the first one including ten patients of 56±14 years and 65±5 kg, and the second one with 10 patients (12 episodes of peritonitis) aged 52±13 years and 64±8 kg. The treatment consists of administering and retaining for 6 h in the peritoneal cavity a solution containing 2 g of vancomycin and 1 g of ceftazidime into 2 l of "dialysis solution". After the antibiotic administration, blood samples were obtained at 4, 6, 8, 10, 24, 48 and 168 h in the first cohort and at 6 and 120 h (C(VAN)(120)) in the second. The pharmacokinetic model was developed from the parameters obtained from the first cohort and was validated by the second cohort, calculating the mean error (ME) and the mean squared prediction error (MSPE) of the C(VAN)(120). RESULTS: Vancomycin serum concentrations fell from 39.63±7.62 mcg/ml at 4h to 8.55±2.87 mcg/ml at 168 h for the first cohort, and from 37.65±6.84 mcg/ml at 6h to 10.82±2.66 mcg/ml at 120 h (C(VAN)(120)) for the second cohort. The pharmacokinetics parameters were: C1=0.006 1/h/kg and Vd:=0.52 1/kg for the first cohort, and C1=0.006 1/h/kg and Vd:=0.53 1/kg for the second. The predictive ME and MSPE of the C(VAN)(120). were 0.59 mcg/ml ([EM*100/C(VAN)(120)=5.5%) and 10.38 mcg(2)/ml(2) ([MES*100/(C(VAN)(120))(2)]) respectively. CONCLUSION: The presented model shows an adequate exactitude and precision for the monitoring of intraperitoneal vancomycin in patients submitted to continuous ambulatory peritoneal dialysis with peritonitis.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Peritoneal Dialysis, Continuous Ambulatory/methods , Vancomycin/administration & dosage , Adult , Aged , Cohort Studies , Drug Monitoring , Female , Humans , Male , Middle Aged , Peritonitis/complications , Prospective Studies , Reproducibility of ResultsABSTRACT
El estudio se ha diseñado con objeto de determinarla interacción entre el ritonavir y el saquinavirdurante su absorción gastrointestinal.Para ello, se han realizado estudios de perfusiónen el intestino delgado completo de ratasWistar, con distintas proporciones de los dosfármacos. Los resultados obtenidos demuestranque la constante aparente de velocidad deabsorción (kap) del ritonavir disminuye, aunqueno significativamente, cuando la concentraciónde saquinavir es al menos un 40% superiora la de ritonavir. Asimismo, la kap saquinavirdisminuye cuando la concentración de ritonavires un 25% superior a la de saquinavir,si bien estas diferencias no son significativas.El mismo comportamiento se observa cuandola concentración de ritonavir es un 40% inferiora la de saquinavir, lo que indicaría que la incorporacióndel saquinavir se modifica por el ritonavir.Se requieren estudios adicionales paradilucidar el mecanismo concreto de interacciónentre los dos fármacos
The study has been designed in order to determinatethe interaction between the ritonavirand the saquinavir during its gastrointestinalabsorption. For it, perfusion studies have beencarried out in the whole intestine of the Wistarrats, with different proportions of the two drugs.The results obtained demonstrate that the apparentabsorption rate constant (kap) of the ritonavirit diminishes, although not significantly,when the saquinavir concentration is at least40% superior to that of ritonavir. Also, the kapsaquinavir diminishes when the ritonavir concentrationis 25% superior to that of saquinavir,although these differences are not significant.The same behavior is observed when the ritonavirconcentration is 40 % smaller to that ofsaquinavir, what would indicate that the incorporationof the saquinavir modifies for the ritonavir.Additional studies are required to elucidatethe concrete mechanism of interactionamong the two drugs
