@article{oai:nagasaki-u.repo.nii.ac.jp:00004711,
 author = {Miyamoto, Hirotaka and Matsueda, Satoshi and Moritsuka, Akihiro and Shimokawa, Kenta and Hirata, Haruna and Nakashima, Mikiro and Sasaki, Hitoshi and Fumoto, Shintaro and Nishida, Koyo},
 issue = {7},
 journal = {Biopharmaceutics & Drug Disposition},
 month = {Oct},
 note = {The effect of hypothermia on the in vivo pharmacokinetics of midazolam was evaluated, with a focus on altered metabolism in the liver and binding to serum proteins. Rat primary hepatocytes were incubated with midazolam (which is metabolized mainly by CYP3A2) at 37, 32 or 28℃. The Michaelis?Menten constant (Km) and maximum velocity (Vmax) of midazolam were estimated using the Michaelis?Menten equation. The Km of CYP3A2 midazolam remained unchanged, but the Vmax decreased at 28℃. In rats, whose temperature was maintained at 37, 32 or 28℃ by a heat lamp or ice pack, the plasma concentrations of midazolam were higher, whereas those in the brain and liver were unchanged at 28℃. The tissue/plasma concentration ratios were, however, increased significantly. The unbound fraction of midazolam in serum at 28?°C was half that at 37℃. These pharmacokinetic changes associated with hypothermic conditions were due to reductions in CYP3A2 activity and protein binding., Biopharmaceutics & Drug Disposition, 36(7), pp.481-489; 2015},
 pages = {481--489},
 title = {Evaluation of hypothermia on the in vitro metabolism and binding and in vivo disposition of midazolam in rats},
 volume = {36},
 year = {2015}
}