Ketamine clearance

Ketamine undergoes hepatic biotransformation in the horse. The primary metabolites are norketamine and dehydronorketamine (Delatour et al 1991, Sams Pizzo 1987, Seay et al 1993). Up to 40% of ketamine can be excreted unchanged in the urine. Upon recovery from ketamine anesthesia, 40% of the ketamine dose still remains in the horse at levels insufficient to produce anesthesia (Kaka et al 1979). In the horse, the elimination half-life of ketamine is reported to be 42-65 min with a total body clearance of 23-26 ml/kg/min (Kaka et al 1979, Waterman et al 1987). 

Chronic renal disease may also affect metabolism, not necessarily because of impaired metabolism in the kidney, but because of an indirect effect of renal failure on liver metabolism. For example, in animals with renal failure it was observed that there was a decrease in hepatic cytochromes P-450 content, and consequently zoxazolamine paralysis time and ketamine narcosis time were prolonged. Cardiac failure may also affect metabolism by altering hepatic blood flow. However even after heart attack without hypotension or cardiac failure, metabolism may be affected. For example, the plasma clearance of lidocaine is reduced in this situation. Other diseases such as those which affect hormone levels hyper- or hypo-thyroidism, lack of or excess growth hormone, and diabetes can alter the metabolism of foreign compounds. 

Ketamine is hepatically metabolized to norketamine, which has reduced CNS activity norketamine is fnrther metabolized and excreted in urine and bile. Ketamine has a large volume of distribution and rapid clearance that make it snitable for continuous infusion withont the drastic lengthening in duration of action seen with thiopental. Protein binding is much lower with ketamine than with the other parenteral anesthetics. 

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