抄録
Use of prescription opioids for cancer pain according to the WHO analgesic ladder has been accepted in Japan. A few clinical reports have been published on interindividual variations in pharmacokinetics of and clinical responses to opioid analgesics in cancer patients. This review summarizes our clinical investigations on analgesics in patients with cancer pain. (1) We evaluated the plasma disposition of oxycodone and its demethylates, and dose escalation based on genetic variants of CYP2D6, CYP3A5, ABCB1 and OPRM1 in cancer patients receiving oxycodone. CYP3A5∗3 altered the plasma disposition of noroxycodone and dose escalation in cancer patients receiving oxycodone. CYP3A5∗3 affected the dose escalation of oxycodone by lowering plasma concentrations of noroxycodone. (2) We evaluated the impact of genetic variants of CYP3A5 and ABCB1 on fentanyl pharmacokinetics and clinical responses after switching to a transdermal system. CYP3A5∗3 and ABCB1 C1236T contribute to interindividual differences in clinical response to the fentanyl transdermal system. These genetic variants may predict clinical response to fentanyl in cancer patients converted to the transdermal system. (3) We evaluated the influence of concomitant administration of gabapentin and magnesium oxide or gabapentin and omeprazole on plasma disposition, intestinal absorption, and urinary excretion of gabapentin in healthy subjects. Concomitant magnesium oxide decreased gabapentin exposure through reducting the extent and rate of intestinal absorption. This reduction may be independent of the suppression of gastrointestinal acidification by antacids. Our findings in this review would contribute to optimizing dosage of analgesics including opioids for patients with cancer pain.
