CAJ | 학술논문

目的：探讨吸烟对利培酮药代动力学和血药浓度的影响，以及利培酮血药浓度与临床疗效及不良反应之间的关系。方法采用反相高效液相色谱法测定利培酮及9-羟利培酮血药浓度，并进行药代动力学参数研究，采用简明精神病症状评定量表（BPRS）、阳性和阴性症状量表（SAPS、SANS）和副反应量表（TESS）评定临床疗效和不良反应。结果吸烟者的利培酮和9-羟利培酮的消除速率较非吸烟者快[消除速率常数（K）更高]，且其消除半衰期（T1/2）较短，达峰浓度（Cmax）和第2周末稳态浓度谷值均较低（P＜0.05或P＜0.01）。利培酮血药浓度及利培酮＋9-羟利培酮总浓度与TESS增分值呈正相关（r=0.42～0.62，均P＜0.01），与BPRS、SANS和SAPS的减分率无显著相关性（P＞0.05）。以治疗8周BPRS总分减分率≥25%为界，划分有效组和无效组进行血药浓度比较，无效组利培酮及利培酮+9-羟利培酮血药浓度低于有效组（P＜0.05）。结论吸烟可加快利培酮的代谢，利培酮和9-羟利培酮总的血药浓度在20～60μg·L-1范围内较为适宜，疗效较好，不良反应较少。
목적：탐토흡연대리배동약대동역학화혈약농도적영향，이급리배동혈약농도여림상료효급불량반응지간적관계。방법채용반상고효액상색보법측정리배동급9-간리배동혈약농도，병진행약대동역학삼수연구，채용간명정신병증상평정량표（BPRS）、양성화음성증상량표（SAPS、SANS）화부반응량표（TESS）평정림상료효화불량반응。결과흡연자적리배동화9-간리배동적소제속솔교비흡연자쾌[소제속솔상수（K）경고]，차기소제반쇠기（T1/2）교단，체봉농도（Cmax）화제2주말은태농도곡치균교저（P＜0.05혹P＜0.01）。리배동혈약농도급리배동＋9-간리배동총농도여TESS증분치정정상관（r=0.42～0.62，균P＜0.01），여BPRS、SANS화SAPS적감분솔무현저상관성（P＞0.05）。이치료8주BPRS총분감분솔≥25%위계，화분유효조화무효조진행혈약농도비교，무효조리배동급리배동+9-간리배동혈약농도저우유효조（P＜0.05）。결론흡연가가쾌리배동적대사，리배동화9-간리배동총적혈약농도재20～60μg·L-1범위내교위괄의，료효교호，불량반응교소。
Objective To evaluate the influence of smoking on the pharmacokinetics and plasma concentrations of risperidone, and to investigate the relationships of blood risperidone concentrations to clinical efficacies and adverse reactions. Methods The plasma concentrations of risperidone and 9-hydroxyrisperidone were measured by RP-HPLC and pharmacokinetic studies were performed in patients. Clinical efficacies and adverse reactions were evaluated with Brief Psychiatric Reacting Scale (BPRS),Scale for the Assessment of Positive Symptoms (SAPS),Scale for the Assessment of Negative Symptoms(SANS) and Treatment Emergent Symptom Scale(TESS). Results Compared with patients who do not smoke, elimination rate constant of risperidone and 9-hydroxyrisperidone increased and elimination half life, peak serum concentrations and valley values of steady-state concentrations at the end of the second week decreased in patients who smoke(P<0.05 or P<0.01).The plasma concentrations of risperidone and the total concentrations of risperidone and 9-hydroxyrisperidone were positively correlated with TESS(r=0.42-0.62,P<0.01),but were not correlated with BPRS,SAPS and SANS(P>0.05). Compared with patients with BPRS total score reduction<25%, the plasma concentrations of risperidone and 9-hydroxyrisperidone significantly decreased in patients with BPRS total score reduction≥25%(P<0.05). Conclusion Smoking accelerates the metabolism of risperidone. The plasma concentrations of risperidone and 9-hydroxyrisperidone in the range of 20-60 μg·L-1 are suitable and effective for the treatment of schizophrenia with less adverse reactions.