Abstract：
BACKGROUND: Intranasal esketamine is an approved drug for treatment‐resistant depression (TRD); however, it is costly and may result in specific adverse effects. In this single case study, we explored if oral esketamine can be a suitable alternative.
METHODS: In collaboration with a 39‐year‐old female with TRD, we compared plasma concentration curves of intranasal (84 mg) and oral (1, 2 and 4 mg/kg) esketamine. Because oral esketamine has a relatively low bioavailability, it results in a different ratio between esketamine and its primary metabolite noresketamine. To increase the bioavailability of oral esketamine, we co‐administered a single dose of the cytochrome P‐450 (CYP) 3A4 inhibitor cobicistat (150 mg).
RESULTS: For all doses administered, oral esketamine resulted in lower esketamine but higher noresketamine peak plasma concentrations compared with intranasal treatment. Using oral esketamine it was not possible to generate a similar esketamine plasma concentration curve as with the intranasal treatment, except when combined with cobicistat (esketamine 2 mg/kg plus cobicistat 150 mg).
CONCLUSIONS: Our findings demonstrate that cobicistat effectively increases the bioavailability of oral esketamine. Further research is required in a larger population, especially to investigate the clinical benefit of cobicistat as a booster drug for oral esketamine.
METHODS: In collaboration with a 39‐year‐old female with TRD, we compared plasma concentration curves of intranasal (84 mg) and oral (1, 2 and 4 mg/kg) esketamine. Because oral esketamine has a relatively low bioavailability, it results in a different ratio between esketamine and its primary metabolite noresketamine. To increase the bioavailability of oral esketamine, we co‐administered a single dose of the cytochrome P‐450 (CYP) 3A4 inhibitor cobicistat (150 mg).
RESULTS: For all doses administered, oral esketamine resulted in lower esketamine but higher noresketamine peak plasma concentrations compared with intranasal treatment. Using oral esketamine it was not possible to generate a similar esketamine plasma concentration curve as with the intranasal treatment, except when combined with cobicistat (esketamine 2 mg/kg plus cobicistat 150 mg).
CONCLUSIONS: Our findings demonstrate that cobicistat effectively increases the bioavailability of oral esketamine. Further research is required in a larger population, especially to investigate the clinical benefit of cobicistat as a booster drug for oral esketamine.
摘要：
背景：鼻内氯胺酮是一种被批准用于治疗难治性抑郁症（TRD）的药物；然而，它是昂贵的，并可能导致特定的不利影响。在这个单一案例研究中，我们探讨了口服esketamine是否可以作为合适的替代方案。
方法：与一名39岁的TRD女性合作，我们比较了鼻内（84mg）和口服（1、2和4mg/kg）艾氯胺酮的血浆浓度曲线。因为口服艾氯胺酮的生物利用度相对较低，它导致艾氯胺酮和其主要代谢产物noresketamine之间的比例不同。为了增加口服艾氯胺酮的生物利用度，我们共同给予单剂量的细胞色素P-450(CYP)3A4抑制剂cobicistat(150mg).
结果：对于所有给药剂量，与鼻内治疗相比,口服艾氯胺酮可降低艾氯胺酮的血浆峰值浓度,但可提高非氯胺酮的血浆峰值浓度.使用口服艾氯胺酮，不可能产生与鼻内治疗相似的艾氯胺酮血浆浓度曲线。除了与cobicistat（艾司氯胺酮2mg/kg加cobicistat150mg）联合使用时。
结论：我们的研究结果表明，柯比司他能有效提高口服艾氯胺酮的生物利用度。需要在更大的人口中进行进一步的研究，特别是研究cobicistat作为口服esketamine的增强药物的临床益处。
方法：与一名39岁的TRD女性合作，我们比较了鼻内（84mg）和口服（1、2和4mg/kg）艾氯胺酮的血浆浓度曲线。因为口服艾氯胺酮的生物利用度相对较低，它导致艾氯胺酮和其主要代谢产物noresketamine之间的比例不同。为了增加口服艾氯胺酮的生物利用度，我们共同给予单剂量的细胞色素P-450(CYP)3A4抑制剂cobicistat(150mg).
结果：对于所有给药剂量，与鼻内治疗相比,口服艾氯胺酮可降低艾氯胺酮的血浆峰值浓度,但可提高非氯胺酮的血浆峰值浓度.使用口服艾氯胺酮，不可能产生与鼻内治疗相似的艾氯胺酮血浆浓度曲线。除了与cobicistat（艾司氯胺酮2mg/kg加cobicistat150mg）联合使用时。
结论：我们的研究结果表明，柯比司他能有效提高口服艾氯胺酮的生物利用度。需要在更大的人口中进行进一步的研究，特别是研究cobicistat作为口服esketamine的增强药物的临床益处。
