TY - JOUR
T1 - Calculating occupancy when one does not have baseline: a comparison of different options
AU - Kim, Euitae
AU - Howes, Oliver D.
AU - Yu, Kyung-Sang
AU - Jeong, Jae Min
AU - Lee, Jae Sung
AU - Jang, In-Jin
AU - Shin, Sang-Goo
AU - Kapur, Shitij
AU - Kwon, Jun Soo
PY - 2011/8
Y1 - 2011/8
N2 - Dopamine D-2 receptor occupancy of antipsychotic drugs is calculated relative to the subject's D-2 receptor binding potential (BP) in the drug-free state (baseline BP). Because baseline BP is seldom known in patients with schizophrenia, population means from unrelated control samples are often used to estimate it. However, this is likely to introduce bias and error into the occupancy measure. There is thus a need for a method to reliably estimate baseline BP for patient populations in whom it may be impractical or unethical to get baseline measurements. It has been previously found that the relationship between plasma concentration and dopamine receptor occupancy by antipsychotic drugs follows a sigmoid E-max model. Based on this, we developed a method for calculating dopamine D-2 receptor occupancy by antipsychotic drugs using an inhibitory E-max model (I-max method) that estimates individual baseline BPs. To validate this, we compared the result from the I-max method with actual occupancy and estimated occupancy calculated from the average baseline BP (substitution method). The data for validation were obtained from two different receptor occupancy studies with the antipsychotic medications YKP1358 and aripiprazole. We estimated the reliability between the true measured occupancy and the predicted occupancy using the intraclass correlation coefficient (ICC), and the variability of occupancy was also compared between the I-max and substitution methods. In YKP1358 study, all the ICCs of the I-max method were above 0.8, but those of the substitution method showed values lower than 0.8. In aripiprazole study, the ICCs of the I-max method were higher than those of the substitution method, but all the ICCs showed higher values than 0.8. The variability of I-max method was significantly smaller than that of substitution method in both studies. The I-max method shows better reliability and less variability than the substitution method. The I-max method can be applied for receptor occupancy study, and bring more reliability and accuracy to the occupancy study in patients with schizophrenia. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1760-1767; doi:10.1038/jcbfm.2011.54; published online 27 April 2011
AB - Dopamine D-2 receptor occupancy of antipsychotic drugs is calculated relative to the subject's D-2 receptor binding potential (BP) in the drug-free state (baseline BP). Because baseline BP is seldom known in patients with schizophrenia, population means from unrelated control samples are often used to estimate it. However, this is likely to introduce bias and error into the occupancy measure. There is thus a need for a method to reliably estimate baseline BP for patient populations in whom it may be impractical or unethical to get baseline measurements. It has been previously found that the relationship between plasma concentration and dopamine receptor occupancy by antipsychotic drugs follows a sigmoid E-max model. Based on this, we developed a method for calculating dopamine D-2 receptor occupancy by antipsychotic drugs using an inhibitory E-max model (I-max method) that estimates individual baseline BPs. To validate this, we compared the result from the I-max method with actual occupancy and estimated occupancy calculated from the average baseline BP (substitution method). The data for validation were obtained from two different receptor occupancy studies with the antipsychotic medications YKP1358 and aripiprazole. We estimated the reliability between the true measured occupancy and the predicted occupancy using the intraclass correlation coefficient (ICC), and the variability of occupancy was also compared between the I-max and substitution methods. In YKP1358 study, all the ICCs of the I-max method were above 0.8, but those of the substitution method showed values lower than 0.8. In aripiprazole study, the ICCs of the I-max method were higher than those of the substitution method, but all the ICCs showed higher values than 0.8. The variability of I-max method was significantly smaller than that of substitution method in both studies. The I-max method shows better reliability and less variability than the substitution method. The I-max method can be applied for receptor occupancy study, and bring more reliability and accuracy to the occupancy study in patients with schizophrenia. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1760-1767; doi:10.1038/jcbfm.2011.54; published online 27 April 2011
U2 - 10.1038/jcbfm.2011.54
DO - 10.1038/jcbfm.2011.54
M3 - Article
SN - 1559-7016
VL - 31
SP - 1760
EP - 1767
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 8
ER -