Abstract:
:Morphine is one of the strongest analgesics and is commonly used for the treatment of chronic pain. The pharmacokinetic properties of morphine are, in part, modulated by P-glycoprotein (P-gp). We previously reported that intestinal P-gp expression levels are influenced via the activation of inducible nitric oxide synthase (iNOS) in streptozotocin (STZ)-induced diabetic mice. Herein, we examine the analgesic effects of orally administered morphine and its pharmacokinetic properties under diabetic conditions, specifically we focusing on the involvement of intestinal P-gp in a type 1 diabetic mouse model. We assessed the analgesic effect of morphine using the tail-flick test. Serum and brain morphine levels were determined using a HPLC-ECD system. Oral morphine analgesic effects and serum and brain morphine content were significantly increased 9 days after STZ administration. The increase in the analgesic effects of morphine, as well as serum and brain morphine content, was suppressed by aminoguanidine, a specific iNOS inhibitor. Conversely, there were no changes in the analgesic effects obtained with subcutaneous morphine in STZ-treated mice. Our findings suggest that the analgesic effects of oral morphine are dependent on intestinal P-gp expression, and this may be one of the reasons that it is difficult to obtain stable pharmacological effects of morphine in diabetic patients.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Nawa A,Fujita-Hamabe W,Kishioka S,Tokuyama Sdoi
10.2133/dmpk.dmpk-11-rg-051subject
Has Abstractpub_date
2011-01-01 00:00:00pages
584-91issue
6eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/DMPK-11-RG-051journal_volume
26pub_type
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