Postmortem changes in tissue concentrations of triazolam and diazepam in rats.
The aim of this study was to investigate the postmortem changes of concentrations of triazolam and diazepam in the rat model and to confirm the factor causing the phenomenon. We administered triazolam or diazepam orally to rats and then sacrificed them 1 h after administration. Abdominal tissues including stomach content and small intestine, thigh muscle and heart blood were collected at 0, 12, 24 h after death, and postmortem changes of the two drug concentrations were compared. Drug concentrations in the samples were analyzed by a selected ion monitoring of gas chromatography/mass spectrometry. Gastrointestinal postmortem concentrations of triazolam and diazepam decreased. On the other hand, the drug concentrations in the liver and kidney increased markedly, and those in lung and heart blood increased slightly during postmortem periods by diffusion from the gastrointestinal tract. The patterns of both drug concentration changes were similar. However, the extent of the triazolam increase tended to be larger than that of diazepam. This difference may be accounted for by lower triazolam concentrations before death. The postmortem drug concentrations of thigh muscle did not change when administered with triazolam and diazepam. For both triazolam and diazepam, a significant correlation was observed in the drug concentration between the small intestine and the kidney at 24 h after death, indicating that major cause of the change in the drug concentration in the kidney was diffusion from the small intestine up to 24 h after death. The results in this study indicate that diazepam as well as triazolam diffuses from the gastrointestinal tract into the surrounding tissues after death and suggest that the diffusion is influenced by their pharmaceutical properties before death.
Shiota
Hideo
H
Department of Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. mikirou@net.nagasaki-u.ac.jp
Nakashima
Mikiro
M
Terazono
Hideyuki
H
Sasaki
Hitoshi
H
Nishida
Koyo
K
Nakamura
Junzo
J
Taniyama
Kotaro
K
D000818:Animals; D014151:Anti-Anxiety Agents / Q000032:analysis / Q000493:pharmacokinetics*; D003975:Diazepam / Q000032:analysis / Q000493:pharmacokinetics*; D005554:Forensic Medicine; D008401:Gas Chromatography-Mass Spectrometry; D005766:Gastrointestinal Contents / Q000737:chemistry; D007421:Intestine, Small / Q000737:chemistry; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D011180:Postmortem Changes; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014229:Triazolam / Q000032:analysis / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D014229:Triazolam; D003975:Diazepam