Decreased analgesic effect of morphine, but not buprenorphine, in patients with advanced P-glycoprotein(+) cancers

Abstract

Background: P-glycoprotein (P-gp) is expressed on the blood-brain barrier (BBB) and acts as a transporter regulating the analgesic effect of morphine. The P-gp is also expressed by different types of tumors. The aim of this study was to determine the potential association of the P-gp expression in malignant tumors with analgesic effects in patients.

Methods: The P-gp expression in 120 malignant tumors was examined by immunohistochemistry. The analgesic responses of individual patients to morphine and buprenorphine (BNP) were evaluated by visual analog scale (VAS). The levels of plasma morphine and BNP were determined by HPLC.

Results: We found that there was no significant difference in the values of VAS between patients with P-gp(+) and P-gp(-) malignant tumors in responses to 0.000025 g x kg(-2) of BNP administered by patient-controlled intravenous analgesia (PCIA), accompanied by similar levels of plasma BNP in those patients. In contrast, the values of VAS in response to 0.00075 g x kg(-2) of morphine in patients with P-gp(+) tumors were significantly greater than those in the patients with P-gp(-) tumors, although similar levels of plasma morphine were detected in both groups of patients. Furthermore, treatment with a higher dose (0.0011 g x kg(-2)) of morphine effectively controlled pain in those with P-gp(+) tumors.

Conclusion: Our data indicated that patients with P-gp(+) tumors required a higher dose of morphine to achieve an analgesic effect and that the P-gp expression in tumors may be valuable for predicting the analgesic responses of patients with severe pain to morphine.