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Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children.

Publication ,  Journal Article
Hornik, CP; Gonzalez, D; van den Anker, J; Atz, AM; Yogev, R; Poindexter, BB; Ng, KC; Delmore, P; Harper, BL; Melloni, C; Lewandowski, A ...
Published in: J Clin Pharmacol
August 2018

Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown. We performed 2 prospective PK studies of ketamine in children receiving either intramuscular or intravenous ketamine and combined the data to develop a pediatric population PK model using nonlinear mixed-effects methods. We applied our model by performing dosing simulations targeting plasma concentrations previously associated with analgesia (>100 ng/mL) and anesthesia awakening (750 ng/mL). A total of 113 children (50 intramuscular and 63 intravenous ketamine) with a median age of 3.3 years (range 0.02 to 17.6 years), and median weight of 14 kg (2.4 to 176.1) contributed 275 plasma samples (149 after intramuscular, 126 after intravenous ketamine). A 2-compartment model with first-order absorption following intramuscular administration and first-order elimination described the data best. Allometrically scaled weight was included in the base model for central and peripheral volume of distribution (exponent 1) and for clearance and intercompartmental clearance (exponent 0.75). Model-estimated bioavailability of intramuscular ketamine was 41%. Dosing simulations suggest that doses of 2 mg/kg intravenously and 8 mg/kg or 6 mg/kg intramuscularly, depending on age, provide adequate sedation (plasma ketamine concentrations >750 ng/mL) for procedures lasting up to 20 minutes.

Duke Scholars

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

August 2018

Volume

58

Issue

8

Start / End Page

1092 / 1104

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Hornik, C. P., Gonzalez, D., van den Anker, J., Atz, A. M., Yogev, R., Poindexter, B. B., … Pediatric Trial Network Steering Committee, . (2018). Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children. J Clin Pharmacol, 58(8), 1092–1104. https://doi.org/10.1002/jcph.1116
Hornik, Christoph P., Daniel Gonzalez, John van den Anker, Andrew M. Atz, Ram Yogev, Brenda B. Poindexter, Kee Chong Ng, et al. “Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children.J Clin Pharmacol 58, no. 8 (August 2018): 1092–1104. https://doi.org/10.1002/jcph.1116.
Hornik CP, Gonzalez D, van den Anker J, Atz AM, Yogev R, Poindexter BB, et al. Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children. J Clin Pharmacol. 2018 Aug;58(8):1092–104.
Hornik, Christoph P., et al. “Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children.J Clin Pharmacol, vol. 58, no. 8, Aug. 2018, pp. 1092–104. Pubmed, doi:10.1002/jcph.1116.
Hornik CP, Gonzalez D, van den Anker J, Atz AM, Yogev R, Poindexter BB, Ng KC, Delmore P, Harper BL, Melloni C, Lewandowski A, Gelber C, Cohen-Wolkowiez M, Lee JH, Pediatric Trial Network Steering Committee. Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children. J Clin Pharmacol. 2018 Aug;58(8):1092–1104.

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

August 2018

Volume

58

Issue

8

Start / End Page

1092 / 1104

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences