POPULATION PHARMACOKINETIC MODELING OF PYRIMETHAMINE (PYR) DURING THE TREATMENT OF CONGENITAL TOXOPLASMOSIS IN PEDIATRICS.

MARSON ELENA; PROSPITTI ANABELA; MASTRANTONIO, GUIDO; FLEITAS, ULISES; PEREZ MONTILLA CARLOS; MORONI SAMANTA; ALTCHEH JAIME; MOSCATELLI, GUILLERMO; GARCÍA-BOURNISSEN, FACUNDO

Congreso; Reunion anual Sociedades de Biociencia, SAIC; 2019

Infection with Toxoplasma gondii, is one of the most widespread zoonoses in the world. Particularly risky is congenital form (CT) with a global risk of transmission by this route of about 40 %, reaching 90 % in the last month of pregnancy. Children with CT receive treatment, usually PYR and sulfadiazine, to prevent morbidity. The current therapy in pediatric patients is protocolized, but due to the absence of pediatric formulations the drugs are prepared in the hospital pharmacy in the form of syrup and at the moment, pharmacological parameters of these drugs have not been corroborated in patients, especially PYR. The objective of this study was to evaluate the pharmacokinetics of PYR in the treatment of pediatric toxoplasmosis, from a population approach(Pop-PK). The study was approved by the institutional ethics committee of the HNRG, including the informed consent for the use of the samples. Residual blood samples (taken for routine clinical procedures) were obtained from 12 pediatric patients undergoing treatment with PYR (0.77-2.7 mg/kg/day), and followed-up in the Parasitology service of the Ricardo Gutiérrez Children's Hospital (HNRG). PYR was quantified on 60 serum samples by high performance reverse chromatography coupled to tandem mass spectrometry (Shimadzu Nexera and Sciex qTrap6500). For the analysis of Pop-PK and the evaluation of pharmacokinetic models, Monolix® was used. Akaike´s information criteria and Bayesian information criteria were selected as statistical criteria for the selection of the best model. The results obtained in the Pop-PK modeling proposed a one-compartmental (Vp= 1.05 L) model with first-order absorption (Kap= 0.843 h-1) and linear elimination (Kep= 0.00531 h-1), with weight-dependent distribution volume (= 0.349 L/Kg). Other more complex models did not result in an improvement in fit and were discarded. Pharmacokinetic studies reported for PYR that differ in populations, set of drugs used and treatment times, propose similar results when comparing Ka and Ke for the pediatric population, but were found to be significantly different from those evaluated for the adult population.