• Mohammed H Elkomy, Nabil Alruwaili, Mohammed Elmowafy, Khaled Shalaby, David R Drover, and Chandra Ramamoorthy.
• Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.
• Pharmacotherapy. 2019 Apr 1; 39 (4): 454-462.

BackgroundAlthough few studies have used ketamine for induction and maintenance of pediatric anesthesia, official dosage recommendations are lacking. This study evaluates the outcomes of adult anesthetic doses in a pediatric population through pharmacokinetic modeling and computer simulations in an attempt to recommend an adequate ketamine dosing regimen.MethodsKetamine plasma concentration-time data in 19 children (age 8 months to 16 years; weight 5.5 to 67 kg) were analyzed according to a non-compartmental pharmacokinetic approach. The relationship between pharmacokinetic parameters and demographic covariates was mathematically characterized. A one-compartment open model was implemented to simulate the plasma profile following administration of 1-4.5 mg/kg IV bolus dose and 0.1-0.5 mg/kg/min continuous infusion of ketamine and to predict anesthesia onset and offset.Key ResultsPharmacokinetic parameters determined were clearance 0.025 ± 0.008 L/kg/min; distribution volume 3.3 ± 1.3 L/kg; half-life 2.6 ± 1 h; and mean residence time 2.3 ± 0.64 h. Body weight was the best predictor of clearance and distribution volume according to a 0.75-power model. Using weight to scale doses was associated with limited variability in simulated concentrations. Ketamine administered as 2.25 mg/kg IV bolus dose, followed by 0.1 mg/kg/min continuous IV infusion enables anesthesia initiation within 3 minutes and maintains it for 3 hours.Conclusions & InferencesWeight-based dosing minimizes age-dependent variation in the plasma concentration of ketamine. Low-to-intermediate adult doses are suitable for induction and maintenance of safe anesthesia in children undergoing short-term surgical operations. However, this finding requires validation in controlled clinical trials before it is adopted into surgical standard practices.© 2019 Pharmacotherapy Publications, Inc.

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