Intramuscular Ketamine Pharmacokinetics in Humans: A Review

For over 50 years, ketamine has been approved for anesthesia and indicated for analgesia. In recent years, new clinical uses of ketamine have become increasingly common and continue to emerge. Intramuscular administration is a main route of administration and is particularly important in situations where resources are limited, such as in emergencies and low-income areas. The goal of this review is to summarize the literature on the pharmacokinetics of intramuscular ketamine in humans. Ten studies assessing intramuscular ketamine pharmacokinetics were identified. These studies looked at doses between 0.1 and 6.0 mg/kg in both healthy volunteers and clinical patients, and in adults and children. The pharmacokinetics of intramuscular ketamine were found to be dose-dependent, with maximal plasma concentrations linearly increasing from 27 ng/mL at a dose of 0.1 mg/kg to 1970 ng/mL at a dose of 6.0 mg/kg. The time to maximal plasma concentration ranged from 10 to 30 min and was largely uncorrelated with dose. The bioavailability of intramuscular ketamine remains unclear, with reported values of 41.1-93.0%. Children displayed faster absorption than adults, and possibly higher and faster norketamine concentrations, but otherwise similar ketamine kinetics. Additional pharmacokinetic data, especially at higher doses of ketamine (> 1.0 mg/kg), are needed to better inform dosing in emerging and diverse clinical uses and scenarios.