RESUMEN
Gentamicin has proven to be a very successful treatment for bacterial infection, but it also can cause adverse effects, especially ototoxicity, which is irreversible. Therapeutic drug monitoring (TDM) in saliva is a more convenient non-invasive alternative compared to plasma. A physiologically-based pharmacokinetic (PBPK) model of gentamicin was built and validated using previously-published plasma and saliva data. The validated model was then used to predict experimentally-observed plasma and saliva gentamicin TDM data in Jordanian pediatric preterm infant patients measured using sensitive LCMS/MS method. A correlation was established between plasma and saliva exposures. The developed PBPK model predicted previously reported gentamicin levels in plasma, saliva and those observed in the current study. A good correlation was found between plasma and saliva exposures. The PBPK model predicted that gentamicin in saliva is 5-7 times that in plasma, which is in agreement with observed results. Saliva can be used as an alternative for TDM of gentamicin in preterm infant patients. Exposure to gentamicin in plasma and saliva can reliably be predicted using the developed PBPK model in patients.
Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Monitoreo de Drogas/métodos , Gentamicinas/farmacocinética , Modelos Biológicos , Ototoxicidad/prevención & control , Infecciones Bacterianas/sangre , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Relación Dosis-Respuesta a Droga , Cálculo de Dosificación de Drogas , Monitoreo de Drogas/instrumentación , Femenino , Gentamicinas/administración & dosificación , Gentamicinas/efectos adversos , Gentamicinas/aislamiento & purificación , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Jordania , Límite de Detección , Masculino , Ototoxicidad/sangre , Ototoxicidad/etiología , Plasma/química , Saliva/química , Eliminación Salival/fisiología , Espectrometría de Masas en Tándem/instrumentación , Espectrometría de Masas en Tándem/métodosRESUMEN
INTRODUCTION: Respiratory distress syndrome (RDS) is defined as acute respiratory distress caused by surfactant deficiency that disturbs gas exchange in preterm infants. It is one of the most common neonatal problems and has been considered to be the most common cause of mortality and morbidity in preterm babies. AIM: In this study, different variables were studied to predict factors for INSURE failure that might help in choosing infants for this procedure early. METHODS: Sixty three (63) patients were enrolled in this study as they met the inclusion criteria. All neonates were intubated briefly less than 2 hours, given natural surfactant in the dose of 3 ml/kg. As soon as it was appropriate and the neonate was stable in the form of normal heart rate and oxygenation, extubation was done and the baby connected to NCPAP at a pressure of 6 cmH2O. INSURE failure was considered if the patient needed mechanical ventilation for more than 72 hours while INSURE success was considered if we were able to wean the patient from CPAP or if the patient didn't need mechanical ventilation in the first 72 hours after surfactant administration. The indications for mechanical ventilation after INSURE procedure were respiratory distress with desaturation (02 sat less than 90%), recurrent apnea, Pco2 more than 60 mmHg. RESULTS: Since INSURE procedure is being largely applied in the neonatal intensive care units, it is important to determine the candidate neonate for this procedure with the minimum failure rate. Although the sample of our study is small, but we can suggest that neonate with gestational age less than 28, birth weight less than 1000 gm, umbilical PH of less than 7, low Apgar score and anemic patients are at high risk for INSURE failure. CONCLUSION: Early diagnosis of PDA and IVH is essential to avoid INSURE method in these patients.
Asunto(s)
Enfermedades del Prematuro/terapia , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Protocolos Clínicos , Femenino , Edad Gestacional , Humanos , Recién Nacido , Intubación Intratraqueal , Masculino , Surfactantes Pulmonares/uso terapéutico , Respiración Artificial , Resultado del TratamientoRESUMEN
BACKGROUND: Few published data exist to guide interpretation of coagulation times in extremely premature infants. OBJECTIVE: To determine coagulation reference ranges on day 1 of life in extremely premature infants. METHODS: A retrospective review of day 1 coagulation tests was performed in 144 infants <27 weeks' gestation between 2004 and 2010 in a tertiary neonatal unit. Samples were drawn through a non-heparinized umbilical or peripheral venous catheter as part of routine clinical care. RESULTS: Mean (SD) and median (range) prothrombin times (PT) of 21.5 (5.3) and 20.2 (13.3-39) s, respectively, activated partial thromboplastin times (APTT) of 75.2 (27.8) and 67.4 (34.9-191.6) s, respectively, and plasma fibrinogen levels of 1.9 (1.1) and 1.4 (0.5-4.8) g/l, respectively, were reported. Using reference intervals derived from the 2.5th to 97.5th centiles, ranges of 14.4-36.7 s, 40.5-158.5 s and 0.7-4.8 g/l were determined for PT, APTT and plasma fibrinogen levels, respectively. In a subcohort with grade 0-2 intraventricular haemorrhage (n = 92), mean PT and APTT were 20.9 and 71.3 s, respectively, versus mean PT and APTT of 23.1 and 88.4 s (p = 0.06 and p = 0.03), respectively for those with grade 3-4 intraventricular haemorrhage. Mean PT and APTT in a cohort of infants defined to be small for gestational age were 22 and 76.8 s. These results did not differ significantly from non-small for gestational age infants, with a mean PT and APTT of 19.5 and 73.4 s (p = 0.09 and p = 0.7). CONCLUSIONS: Reference ranges based on retrospective data were determined for PT, APTT and fibrinogen in a large cohort of extremely preterm infants.