title: Population pharmacokinetics of ketamine in children with heart disease.
abstract: This study aims at developing a population pharmacokinetic model for ketamine in children with cardiac diseases in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Twenty-one children (6 months to 18 years old) were enrolled in this prospective, open label study. Ketamine 2mg/kg IV was administered and blood samples were then collected over 8h for ketamine assay. Pharmacokinetic data analysis using NONMEM, was undertaken. Ketamine pharmacokinetics was adequately described by a two-compartment linear disposition model. Typical population parameters were: total clearance: 60.6 ×(weight/70)(0.75)L/h, intercompartmental clearance: 73.2 ×(weight/70)(0.75)L/h, central distribution volume: 57.3 ×(weight/70)L, and peripheral distribution volume: 152 ×(weight/70)L. Ketamine clearance in children with pre-existing congenital heart disease was comparable to values reported in healthy subjects. Computer simulations indicated that an initial loading dose of ketamine 2mg/kg IV over 1 min followed by a constant rate infusion of 6.3mg/kg/h for 29 min, 4.5mg/kg/h from 30 to 80 min, and 3.9 mg/kg/h from 80 to 120 min achieves and maintains anesthetic plasma level for 2h in children 1 year or older (weight ≥ 10 kg).
authors.affiliation: Department of Anesthesia, 300 Pasteur Drive, Stanford University, Stanford, CA 94305-5640, USA; Department of Pharmaceutics and Industrial Pharmacy, Beni Suef University, Beni Suef, Egypt.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Elkomy
authors.affiliation: Department of Anesthesia, 300 Pasteur Drive, Stanford University, Stanford, CA 94305-5640, USA. Electronic address: ddrover@stanford.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Drover
authors.affiliation: Department of Anesthesia, 300 Pasteur Drive, Stanford University, Stanford, CA 94305-5640, USA.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Hammer
authors.affiliation: University of Colorado at Denver Health Science Center, Aurora, CO 80045, USA.
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Galinkin
authors.affiliation: Department of Anesthesia, 300 Pasteur Drive, Stanford University, Stanford, CA 94305-5640, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Ramamoorthy
mesh_terms: D000293:Adolescent; D000778:Anesthetics, Dissociative / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007649:Ketamine / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine
keywords: Children; Ketamine; NONMEM; Pharmacokinetics