PT  - JOURNAL ARTICLE
AU  - KIMURA, YOSHIAKI
AU  - SHIBATA, MIKA
AU  - TAMADA, MIKA
AU  - OZAKI, NORIYUKI
AU  - ARAI, KUNIZO
TI  - Pharmacokinetics of Morphine in Rats with Adjuvant-induced Arthritis
DP  - 2017 Sep 01
TA  - In Vivo
PG  - 811--817
VI  - 31
IP  - 5
4099  - http://iv.iiarjournals.org/content/31/5/811.short
4100  - http://iv.iiarjournals.org/content/31/5/811.full
SO  - In Vivo2017 Sep 01; 31
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