Otani K, Tybring G, Mihara K, Yasui N, Kaneko S, Ohkubo T, Nagasaki T, Sugawara K
Department of Neuropsychiatry, Hirosaki University Hospital, Japan.
Eur J Clin Pharmacol. 1998 Jan;53(5):347-9. doi: 10.1007/s002280050391.
The correlations between steady-state plasma concentrations of mianserin and its active metabolite desmethylmianserin and those of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were examined in 19 depressed patients.
Ten patients received first mianserin (30 mg per day) and second trazodone (150 mg per day), while 9 patients received these treatments in the opposite sequence, with at least 2-week intervals between the two phases. Blood was sampled at steady state, 1-3 weeks after initiation of each treatment. Plasma concentrations of mianserin, the separate enantiomers S(+)- and R(-)-mianserin, desmethylmianserin, trazodone and m-CPP were measured by means of high-performance liquid chromatography.
There was a significant correlation between steady-state plasma concentrations of trazodone and total mianserin (r = 0.59) or S(+)-mianserin (r = 0.57), but not R(-)-mianserin (r = 0.33).
The present study thus suggests that the metabolic capacity of mianserin, especially the more active S(+)-enantiomer, and that of trazodone correlate to each other. This finding supports the previous suggestions that cytochrome P4502D6 is involved in the metabolism of mianserin and trazodone.
在19名抑郁症患者中研究米安色林及其活性代谢物去甲米安色林的稳态血浆浓度与曲唑酮及其活性代谢物间氯苯哌嗪(m-CPP)的稳态血浆浓度之间的相关性。
10名患者先服用米安色林(每日30毫克),后服用曲唑酮(每日150毫克),而9名患者则按相反顺序接受这些治疗,两个阶段之间至少间隔2周。在每种治疗开始后1 - 3周的稳态时采集血样。通过高效液相色谱法测定米安色林、单独的对映体S(+)-米安色林和R(-)-米安色林、去甲米安色林、曲唑酮和m-CPP的血浆浓度。
曲唑酮的稳态血浆浓度与总米安色林(r = 0.59)或S(+)-米安色林(r = 0.57)之间存在显著相关性,但与R(-)-米安色林(r = 0.33)不存在显著相关性。
本研究因此表明米安色林,尤其是活性更强的S(+)-对映体的代谢能力与曲唑酮的代谢能力相互关联。这一发现支持了先前关于细胞色素P4502D6参与米安色林和曲唑酮代谢的推测。