联用抗抑郁药对难治性抑郁症患者中艾氯胺酮药代动力学特征的潜在影响
The Potential Influence of Associated Antidepressants on the Pharmacokinetic Profile of Esketamine in Patients Affected by Treatment-resistant Depression.
作者信息
Alborghetti Marika, Lionetto Luana, Lombardozzi Ginevra, Montaguti Luca, Trovini Giada, Donato Daniela, Costanzi Giuseppe, Bernardini Donatella De, Catapano Federica, Surano Michele, Pagano Ilaria, Ceccherelli Alessia, Bianchini Edoardo, Di Lorenzo Giorgio, Simmaco Maurizio, Martinotti Giovanni, Kotzalidis Georgios D, Nicoletti Ferdinando, Filippis Sergio De
机构信息
Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Clinical Biochemistry, Mass Spectrometry Section, Sant'Andrea University Hospital, Rome, Italy.
出版信息
Curr Neuropharmacol. 2025;23(10):1301-1312. doi: 10.2174/011570159X356952241216172603.
INTRODUCTION/OBJECTIVE: Esketamine is administered intranasally in combination with at least another antidepressant in patients with treatment-resistant depression. Some of these antidepressants might affect ketamine's pharmacokinetic profile by inhibiting cytochrome-P (CYP) isoforms. Our aim was to establish how different types of combined antidepressants affect serum and salivary levels of esketamine at the time of maximum plasma concentrations and afterward in TRD patients receiving esketamine in a real-world context.
METHODS
Serum and salivary samples were collected from 53 patients receiving intranasal esketamine (56 mg) at baseline, after 20 min (roughly corresponding to T), 7 hours (corresponding to the t value), 24, and 72 hours. Patients were stratified according to the combined antidepressant medication.
RESULTS
Salivary esketamine levels were several-fold higher than the corresponding serum levels at all time points, and showed high inter-individual variability. Serum 20-min post-esketamine levels and AUC levels were significantly higher in patients on antidepressants known to inhibit different isoforms of CY (paroxetine, fluoxetine, duloxetine, venlafaxine), with respect to levels detected in patients on sertraline, citalopram, escitalopram, vortioxetine. These changes in the pharmacokinetic profile of esketamine did not affect the clinical outcome of esketamine. However, changes in systolic blood pressure in response to esketamine positively correlated with serum esketamine levels, suggesting a reduction of esketamine dose in patients with cardiovascular comorbidity under treatment with paroxetine, fluoxetine, duloxetine, venlafaxine.
CONCLUSION
The CY-related status of co-administered antidepressants may affect esketamine levels. However, the small sample sizes of the co-administered drug subgroups and multiple prescriptions do not allow for drawing strong conclusions.
引言/目的：在难治性抑郁症患者中，艾氯胺酮通过鼻内给药，与至少另一种抗抑郁药联合使用。这些抗抑郁药中的一些可能通过抑制细胞色素P（CYP）同工酶来影响氯胺酮的药代动力学特征。我们的目的是确定在现实环境中，接受艾氯胺酮治疗的难治性抑郁症患者在血浆浓度达到峰值时及之后，不同类型的联合抗抑郁药如何影响艾氯胺酮的血清和唾液水平。
方法
收集53例接受鼻内艾氯胺酮（56mg）治疗的患者在基线、20分钟后（大致对应T）、7小时（对应t值）、24小时和72小时的血清和唾液样本。患者根据联合使用的抗抑郁药物进行分层。
结果
在所有时间点，唾液中艾氯胺酮水平均比相应的血清水平高几倍，且个体间差异较大。已知抑制CY不同同工酶的抗抑郁药（帕罗西汀、氟西汀、度洛西汀、文拉法辛）治疗的患者，艾氯胺酮给药后20分钟血清水平和AUC水平显著高于舍曲林、西酞普兰、艾司西酞普兰、伏硫西汀治疗的患者。艾氯胺酮药代动力学特征的这些变化并未影响艾氯胺酮的临床疗效。然而，艾氯胺酮引起的收缩压变化与血清艾氯胺酮水平呈正相关，提示在接受帕罗西汀、氟西汀、度洛西汀、文拉法辛治疗且合并心血管疾病的患者中应减少艾氯胺酮剂量。
结论
联合使用的抗抑郁药与CY相关的状态可能影响艾氯胺酮水平。然而，联合用药亚组的样本量较小且存在多种处方情况，因此无法得出强有力的结论。
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