Development of Physiologically Based Pharmacokinetic Model and Assessment of the Impact of Renal Underdevelopment in Preterm Infants on the Pharmacokinetics of Aminophylline

Objective:To develop a physiologically based pharmacokinetic (PBPK) model for individualization of the dosing regimen considering the physiological requirements of these preterm neonates. Methods: The study comprised preterm newborns with fewer than 34 weeks of gestation and six apneic episodes in 24 h. A PBPK model was created using PK-SIM (version 9, update 1, GitHub, San Francisco, CA, USA). A PBPK model is built using a typical loading dosage of 5 mg/kg and a maintenance dose of 1.5 mg/kg. Based on the verified base model, a PBPK model representing renal underdevelopment based on nRIFLE/pRIFLE categorization was developed. Results: The PK parameters of Aminophylline were computed using the PBPK model. As per the model prediction, T1/2 and area under the curve reduced as postnatal age increased, and in the event of renal underdevelopment, even while Cmax for patients under R (RISK), I (injury) was within the therapeutic range; it was greater compared to preterm without any renal complications. Mean Cmax (mol/L) was 59.53 and for R, I, and F (FAILURE) categories the values were 83.04, 99.69, and 126.98, respectively. Conclusion: The model was created using appropriate drug, study subject, and dosage protocol inputs. The established PBPK model could help in individualizing aminophylline dose in preterm babies.

Short chain acyl Co-A dehydrogenase deficiency a rare inborn error of metabolism.

Background & objectives: Short chain acyl coenzyme A dehydrogenase deficiency (SCADD) is a rare autosomal recessive inborn error of mitochondrial fatty acid β oxidation. The energy producing fatty acid oxidation pathway is affected at the first step due to deficiency of short chain acyl coA dehydrogenase and is manifested as lethargy, metabolic acidosis and hypoglycaemia. We report a case ofeight day old male neonate born to 32 year old female by caesarean delivery diagnosed with SCADD. Investigations: Blood investigations of haematology, serum electrolytes, and enzymes levels were done. Metabolic screening for TSH, galactosaemia, blood ammonia was also conducted. Results: Serum sample revealed elevated acyl carnitine levels and urine analysis for organic acid showed slightly elevated Methyl malonic acid. The neonate was mechanically ventilated and metabolic acidosis was corrected with 8.4 % sodium bicarbonate andintravenous dextrose. Carnitor syrup 5ml/500mg was started once daily and the neonate improved in general activity along with weight gain. Conclusion: Neonatal screening by biochemical method facilitates earlier diagnosis and, along with effective management prevents morbidity and prolongs survival.

Opsismodysplasia.

Opsismodysplasia is a rare osteochondrodysplasia with micromelia and platyspondyly. The authors report on a neonate with opsismodysplasia. During the antenatal period, polyhydramnios was noted. This is the first report of opsismodysplasia from India. Significant observation was antenatal polyhydramnios.

Neonatal arrhythmia with diaphragmatic eventration.

Supraventricular tachycardia is the most common symptomatic arrhythmia in young patients, frequently associated with Wolff-Parkinson-White (WPW) syndrome. We report a case of supraventricular tachycardia with Wolff-Parkinson-White (WPW) syndrome associated with partial eventration of a diaphragm in a neonate.

Neonate subcapsular splenic hematoma.

Splenic hematoma is an unusual event in newborn babies. The present study report a two day old infant who presented to us in shok with severe pallor and abdominal distension. Initially ultrasonography of evaluation by ultrasound (US) revealed a left adrenal hemorrhage but was subsequently confirmed to be a subcapsular splenic hematoma by computed tomography (CT) scan of the abdomen. This article highlights the utility of CT scan in diagnosis although review of literature shows ultrasonography to be primary screening investigative modality for abdominal visceral bleeds in the neonatal period.