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• W2316248091 abstract "Ketamine is an injectable anesthetic that inhibits n-methyl-D-aspartate (NMDA) receptors. At doses smaller than the anesthetic dose, it has recently been shown to decrease neuropathic pain, such as postherpetic neuralgia, which does not respond to nonsteroidal anti-inflammatory drugs or opioid analgesics. Furthermore, its main metabolite, norketamine, has also been reported to contribute to the analgesic effect. However, since ketamine is available only in an injectable form, the development of new formulations for outpatient use has been eagerly awaited. With this in mind, we developed non-injectable ketamine preparations for neuropathic pain relief, determined their theoretical dosage regimen, and prepared information on their proper use.The non-injectable preparations we made were oral tablets (wet-granulation, Formulation 1 ; direct compression, Formulation 2), sublingual tablets, a suppository, and nasal drops (spray). Upon performing various pharmaceutical property tests on the two types of oral tablets, we found that Formulation 1 was superior to Formulation 2 in this respect. We also measured the plasma concentrations of ketamine and norketamine for each ketamine preparation after administering them to three healthy volunteers, finding that the bioavailability of the oral tablets was the lowest at approximately 20%. The bioavailability of both the sublingual tablets and the suppository was approximately 30%, and that of the nasal drops approximately 45%. Next, after administering 50 mg of each of the preparations, their analgesic effects were predicted by NMDA receptor occupancy with the results suggesting that their analgesic effects were almost equal. Therapy with oral tablets 50 mg tid was predicted to produce a 10% or greater decrease in pain score and when they were administered according to a predetermined regimen to 7 patients with neuropathic pain who gave prior consent, the pain score decreased by 58±12%. Since this value was near the maximum decrease of 72%, a value estimated from simulated plasma concentrations, this dosage regimen seemed to be adequate. A study on the metabolic properties of ketamine suggested that in its n-demethylation (the major metabolic pathway for ketamine), CYP 2 B 6 may represent high-affinity activity, whereas CYP 2 C 9 and CYP 3 A 4 may represent low affinity.Hospitals make their own preparations in cases where the problem cannot be resolved by commercially available drugs but such in-hospital preparations have not been sufficiently studied for safety and effectiveness. In this study, in addition to developing various ketamine preparations for home treatment, we measured changes in plasma concentrations, estimated the analgesic effects, and prepared information on the proper use of ketamine as an analgesic. Our study significantly contributed to the enhancement of QOL in patients with neuropathic pain." @default.
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• W2316248091 date "2006-01-01" @default.
• W2316248091 modified "2023-09-25" @default.
• W2316248091 title "Studies on Development and Clinical Application of Ketamine Preparations for Neuropathic Pain Relief" @default.
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• W2316248091 doi "https://doi.org/10.5649/jjphcs.32.275" @default.
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