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Pharmacokinetic evidence for the long‐lasting effects of nor‐binaltorphimine (nor‐BNI)
Author(s) -
Kishioka Shiroh,
Kiguchi Norikazu,
Kobayashi Yuka,
Ko Mei-Chuan,
Woods James
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb581
Subject(s) - pharmacokinetics , (+) naloxone , chemistry , opioid receptor , antagonist , high performance liquid chromatography , in vivo , endocrinology , pharmacology , medicine , receptor , chromatography , biology , microbiology and biotechnology
It is well known that a single administration of nor‐binaltorphimine (nor‐BNI), which is a kappa opioid receptor antagonist, has long‐lasting effects in vivo . However, there is no direct pharmacokinetic evidence of prolonged effects of this drug. In this experiment, we quantified both serum concentration and brain content of nor‐BNI in mice, using high‐performance liquid chromatography with the electrochemical detector (HPLC‐ECD) method. After subcutaneous injection of a mixture of nor‐BNI (30 mg/kg) and naloxone (30 mg/kg), serum and brain samples were collected at 1 hr, 1, 3, 7, 14, 21 and 28 days. Serum concentrations of nor‐BNI were detected at 1 hr and 1 day after injection in all mice, at day 3 in three out of seven mice, and at day 7 in one out of six mice. After day 14, serum concentrations of nor‐BNI were below the lower limit of detection in all mice. In comparison, nor‐BNI was detected at in the brains of all mice from 1 hr to day 21, and was detected at day 28 in two out of six mice. On the other hand, serum concentrations and brain content of naloxone were detected only at 1 hr after injection and both serum concentrations and brain content were below the lower detection limit after that in all mice. In conclusion, we detected nor‐BNI and naloxone in both blood and brain using HPLC‐ECD method, and provided the pharmacokinetic evidence for the long‐lasting effects of nor‐BNI in vivo .