RT Journal Article
SR Electronic
T1 Pharmacokinetics of Morphine in Rats with Adjuvant-induced Arthritis
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 811
OP 817
VO 31
IS 5
A1 KIMURA, YOSHIAKI
A1 SHIBATA, MIKA
A1 TAMADA, MIKA
A1 OZAKI, NORIYUKI
A1 ARAI, KUNIZO
YR 2017
UL http://iv.iiarjournals.org/content/31/5/811.abstract
AB We investigated the in vivo dynamics and analgesic effect of morphine using an adjuvant-induced arthritis (AA) rat as a model of chronic inflammation. Morphine generally binds to μ-opioid receptors in the brain to exert its effects. After several minutes, it is metabolized by glucuronidation via a UDP-glucuronosyltransferase (UGT). Here, we showed that in AA rats, UGT activity in liver microsomes was reduced. Morphine-free serum fractions in AA rats were also decreased (control, 84.9%; AA, 63.9%) and the expression of ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1), which plays a crucial role in morphine bile excretion, decreased to 23.0% that of the control group. However, we observed no significant difference between the AA and control groups regarding blood concentrations of morphine and morphine-3-glucuronide. In contrast, the analgesic effect of morphine increased 4-fold in AA rats. Our results showed that the pharmacokinetics of morphine is not changed, but the pharmacodynamics of morphine is enhanced in chronic inflammation