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Tomoya Sakurada, Seiji Zusi, Eriko Kobayashi, Nobunori Satoh and Shiro Ueda
Morphine and oxycodone are widely used as analgesic drugs for cancer pain. Frequently, morphine and oxycodone are given alternately to avoid adverse drug reactions. Morphine is metabolized primarily into two glucuronide metabolites, morphine-3-glucuronide and morphine-6-glucuronide to be pharmacologically active. Morphine-3-glucuronide and morphine-6-glucuronide have neuroexcitatory action and analgesic activity, respectively. Oxymorphone, a metabolite of oxycodone, has an analgesic effect, however it is so small that it can be neglected when considering oxycodone. The pharmacological effects of these drugs and also their metabolites have been reported in experimental papers, but in humans, the relationships between these plasma concentrations and the clinical effects remain unclear. Also the necessity for simultaneous determination of both drugs has been suggested because opioid rotation is performed clinically. However, to date there is no study which has simultaneously determined these four drugs, and also achieved a high recovery. In this paper, in order to perform a reliable pharmacokinetic study of cancer pain patients receiving morphine and oxycodone, an easy, rapid, sensitive and selective analytical method was proposed and validated.