Hugo Juárez Olguín1,2, Hector Osnaya Martínez3, Carmen Flores Pérez4, Blanca Ramírez Mendiola4, Liliana Rivera Espinosa4, Juan Luis Chávez Pacheco4, Janett Flores Pérez4,5, Ignacio Mora Magaña6. 1. Laboratory of Pharmacology, National Institute of Pediatrics, Avenida Imán N° 1, 3rd piso Colonia Cuicuilco, CP 04530, Mexico City, Mexico. juarezol@yahoo.com. 2. Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico. juarezol@yahoo.com. 3. Service of Cardiology, National Institute of Pediatrics, Mexico City, Mexico. 4. Laboratory of Pharmacology, National Institute of Pediatrics, Avenida Imán N° 1, 3rd piso Colonia Cuicuilco, CP 04530, Mexico City, Mexico. 5. Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico. 6. Subdirection of Teaching and Educational Programming, National Institute of Pediatrics, Mexico City, Mexico.
Abstract
BACKGROUND: Recently, sildenafil was introduced to treat pulmonary arterial hypertension (PAH); however, there are currently few studies on the pharmacokinetics of sildenalfil in children. Therefore, we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose. METHODS: Twelve children diagnosed with PAH, consisting of with ten males and two females, were recruited for the study after obtaining written consent from their parents or guardians. Blood samples were obtained predose and at 0.25, 0.5, 1, 2, 4, 8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory. The samples were analyzed using a previously validated high performance liquid chromatography method. RESULTS: A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for selecting a more adjustable model was performed. The following pharmacokinetic parameters were obtained: maximal concentration (Cmax): 366±179 ng/mL, time to maximal concentration: 0.92±0.30 hours, elimination half-life (t1/2): 2.41±1.18 hours, total clearance (CLtot/F): 5.85±2.81 L/hour, volume of distribution (Vd/F): 20.13±14.5 L, absorption rate constants (Ka): 0.343 hour-1, elimination rate (Ke): 0.35 hour-1, area under curve from zero to infinity: 2061±618 ng/mL/hour. The data of all patients adjusted to the model of one compartment were corroborated using AIC. CONCLUSIONS: The parameters Ka, Ke and t1/2 were found to be similar to those reported in adults; however, the values of Cmax and Vd/F were significantly higher. Based on these findings, we propose that treatment regimen of sildenafil be adjusted in children with PAH.
BACKGROUND: Recently, sildenafil was introduced to treat pulmonary arterial hypertension (PAH); however, there are currently few studies on the pharmacokinetics of sildenalfil in children. Therefore, we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose. METHODS: Twelve children diagnosed with PAH, consisting of with ten males and two females, were recruited for the study after obtaining written consent from their parents or guardians. Blood samples were obtained predose and at 0.25, 0.5, 1, 2, 4, 8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory. The samples were analyzed using a previously validated high performance liquid chromatography method. RESULTS: A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for selecting a more adjustable model was performed. The following pharmacokinetic parameters were obtained: maximal concentration (Cmax): 366±179 ng/mL, time to maximal concentration: 0.92±0.30 hours, elimination half-life (t1/2): 2.41±1.18 hours, total clearance (CLtot/F): 5.85±2.81 L/hour, volume of distribution (Vd/F): 20.13±14.5 L, absorption rate constants (Ka): 0.343 hour-1, elimination rate (Ke): 0.35 hour-1, area under curve from zero to infinity: 2061±618 ng/mL/hour. The data of all patients adjusted to the model of one compartment were corroborated using AIC. CONCLUSIONS: The parameters Ka, Ke and t1/2 were found to be similar to those reported in adults; however, the values of Cmax and Vd/F were significantly higher. Based on these findings, we propose that treatment regimen of sildenafil be adjusted in children with PAH.
Authors: Christian Apitz; Janette T Reyes; Helen Holtby; Tilman Humpl; Andrew N Redington Journal: J Am Coll Cardiol Date: 2010-04-06 Impact factor: 24.094
Authors: Nazzareno Galiè; Hossein A Ghofrani; Adam Torbicki; Robyn J Barst; Lewis J Rubin; David Badesch; Thomas Fleming; Tamiza Parpia; Gary Burgess; Angelo Branzi; Friedrich Grimminger; Marcin Kurzyna; Gérald Simonneau Journal: N Engl J Med Date: 2005-11-17 Impact factor: 91.245
Authors: Farah Peiravian; Ahmad A Amirghofran; Mohammad Borzouee; Gholam H Ajami; Mohammad R Sabri; Sara Kolaee Journal: Asian Cardiovasc Thorac Ann Date: 2007-04
Authors: Daniel Gonzalez; Matthew M Laughon; P Brian Smith; Shufan Ge; Namasivayam Ambalavanan; Andrew Atz; Gregory M Sokol; Chi D Hornik; Dan Stewart; Gratias Mundakel; Brenda B Poindexter; Roger Gaedigk; Mary Mills; Michael Cohen-Wolkowiez; Karen Martz; Christoph P Hornik Journal: Br J Clin Pharmacol Date: 2019-12-15 Impact factor: 3.716
Authors: Janneke M Brussee; Elke H J Krekels; Elisa A M Calvier; Semra Palić; Amin Rostami-Hodjegan; Meindert Danhof; Jeffrey S Barrett; Saskia N de Wildt; Catherijne A J Knibbe Journal: AAPS J Date: 2019-06-27 Impact factor: 4.009
Authors: Kurayi Mahachi; Joss Kessels; Kofi Boateng; Anne Eudes Jean Baptiste; Pamela Mitula; Ebru Ekeman; Laura Nic Lochlainn; Alexander Rosewell; Samir V Sodha; Bernadette Abela-Ridder; Albis Francesco Gabrielli Journal: Vaccine Date: 2022-08-13 Impact factor: 4.169
Authors: Natalia Sutiman; Janine Cynthia Koh; Kevin Watt; Christoph Hornik; Beverly Murphy; Yoke Hwee Chan; Jan Hau Lee Journal: Front Pediatr Date: 2020-06-26 Impact factor: 3.418