BRIEF COMMUNICATION Characteristics of the relationship between plasma ketamine concentration and its effect on the minimum alveolar concentration of isoflurane in dogs Bruno H Pypendop DrMedVet, DrVetSci, Diplomate ACVA, Adrian Solano DVM, Pedro Boscan DVM, PhD, Diplomate ACVA & Jan E Ilkiw BVSc, PhD, Diplomate ECVA Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA Correspondence: Bruno Pypendop, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA. E-mail: bhpypendop@ucdavis.edu Abstract Objective To characterize the shape of the relation- ship between plasma ketamine concentration and minimum alveolar concentration (MAC) of isoflurane in dogs. Study design Retrospective analysis of previous data. Animals Four healthy adult dogs. Methods The MAC of isoflurane was determined at five to six different plasma ketamine concentrations. Arterial blood samples were collected at the time of MAC determination for measurement of plasma ketamine concentration. Plasma concentration/ef- fect data from each dog were fitted to a sigmoid inhibitory maximum effect model in which MAC c ¼ MAC 0  ðMAC0  MACminÞC  EC  50 þC  , where C is the plasma ketamine concentration, MAC c is the MAC of isoflurane at plasma ketamine concentration C, MAC 0 is the MAC of isoflurane without ketamine, MAC min is the lowest MAC predicted during keta- mine administration, EC 50 is the plasma ketamine concentration producing 50% of the maximal MAC reduction, and c is a sigmoidicity factor. Nonlinear regression was used to estimate MAC min , EC 50 , and c. Results Mean ± SEM MAC min , EC 50 and c were estimated to be 0.11 ± 0.01%, 2945 ± 710 ng mL )1 and 3.01 ± 0.84, respectively. Mean ± SEM maximal MAC reduction predicted by the model was 92.20 ± 1.05%. Conclusions The relationship between plasma keta- mine concentration and its effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction predicted by the model is less than 100%, implying that high plasma ketamine con- centrations may not totally abolish gross purposeful movement in response to noxious stimulation in the absence of inhalant anesthetics. Clinical relevance The parameter estimates reported in this study will allow clinicians to predict the expected isoflurane MAC reduction from various plasma ketamine concentrations in an average dog. Keywords dog, dose–effect relationship, isoflurane, ketamine, minimum alveolar concentration, phar- macodynamics. Introduction Ketamine is a dissociative anesthetic that acts at the phencyclidine site of the N-methyl-D-aspartate receptor where it antagonizes the effect of the exci- tatory amino acid glutamate (Kohrs & Durieux 1998). Ketamine produces anesthesia and analge- sia, and has been reported to decrease the minimum alveolar concentration (MAC) of inhalant anes- thetics in rats, mice, horses, and dogs (White et al. 1975; Daniell 1990; Schwieger et al. 1991; Muir & Sams 1992). We recently reported the effects of 209 Veterinary Anaesthesia and Analgesia, 2007, 34, 209–212 doi:10.1111/j.1467-2995.2006.00324.x