Correlation between drug and metabolite concentrations in plasma and anesthetic action of ketamine in swine

Pharmacokinetic variables and metabolism of IM and IV administered ketamine (15 mg/kg of body weight) were determined in 8 swine (2 adult sows and 6 young pigs). After IM administration, maximal plasma concentration was rapidly reached, but peak concentration varied considerably, although comparison with IV data for the same swine indicated that the drug was almost completely absorbed from the musculature. After IV administration, ketamine kinetics followed a 3-term exponential decrease, indicating rapid initial distribution of the drug to highly vascular tissues including the brain, followed by redistribution into less vascular tissues, and elimination. Redistribution and elimination phases, with similar kinetics as those observed in the IV experiment, also were determined in the IM experiment. After both routes of administration, onset of anesthesia was rapid, and most swine recovered consciousness during the phase of redistribution, indicating that anesthesia is terminated by redistribution of drug from the brain into other tissues, whereas metabolism and excretion are less important for duration of anesthesia induced by ketamine. The time during which the swine resumed a lateral position (sleep time) was positively correlated with plasma ketamine concentration at onset of lateral recumbency, as well as with the area under the plasma concentration-time curve. The minimal plasma ketamine concentration for induction of immobilization was about 2 microgram/ml. In adult sows, ketamine induced profound analgesia, which was not obtained in young pigs; this difference in potency could not be related to pharmacokinetic differences between young and adult swine. With respect to metabolism of ketamine in swine, the major metabolite in plasma was norketamine (metabolite I), whereas a second metabolite (metabolite II) was detected only in low concentrations. Elimination half-life of ketamine was about 2 hours after either IM or IV administration.