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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Modeling chronic olanzapine exposure using osmotic minipumps: pharmacological limitations.
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Modeling chronic olanzapine exposure using osmotic minipumps: pharmacological limitations.

机译：使用渗透微型泵对慢性奥氮平暴露进行建模：药理学限制。

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Animal models can face unique challenges in mirroring what occurs in humans. This is the case for antipsychotics in rodents, where these drugs are metabolized much more rapidly. One strategy to address this issue has been the use of osmotic minipumps to ensure continuous antipsychotic exposure over prolonged intervals, which is routinely the case when these same drugs are administered to humans. More recently, it has been identified that with olanzapine this approach may be compromised by oxidative degradation, a process that can be observed within days. Further, in vivo evidence has reported progressive decreases in plasma levels over a 1-month interval. To address this issue in vitro, osmotic minipumps (n=4), with olanzapine at a concentration resulting in a dose of 7.5mg/kg/day in vivo, were placed in saline-filled Falcon tubes and immersed in a water bath. Olanzapine concentrations were assessed in the minipumps as well as the surrounding water bath at baseline, 1h, and days 1, 7, 14, 21, and 28. Minipump results indicated a monophasic exponential decay and a half-life of 14.8 days (95% CI=13.1-17.1 days). Results from the water bath demonstrated a linear increase in olanzapine up to and including day 21, followed thereafter by a decrease to day 28. It is concluded that administration of olanzapine via osmotic minipump is viable in animal models to mirror what occurs in humans, although the interval should be confined to 2 weeks. As well, strategies in dissolving olanzapine to diminish oxidation are discussed.
机译：动物模型在反映人类发生的事情时可能面临独特的挑战。啮齿动物中的抗精神病药就是这种情况，这些药物的代谢要快得多。解决该问题的一种策略是使用渗透微型泵，以确保长时间连续服用抗精神病药，而对人使用这些相同的药物通常是这种情况。最近，已经确定，使用奥氮平时，这种方法可能会受到氧化降解的损害，这一过程可以在几天之内观察到。此外，体内证据已经报告了在1个月的时间间隔内血浆水平逐渐下降。为了在体外解决该问题，将奥氮平的渗透微型泵（n = 4）的浓度导致体内剂量为7.5mg / kg /天，将其放入充满盐水的Falcon管中并浸入水浴中。在基线，1h和第1、7、14、21和28天时，在小型泵和周围水浴中评估了奥氮平的浓度。小型泵结果表明单相指数衰减，半衰期为14.8天（95％） CI = 13.1-17.1天）。水浴的结果表明，直到第21天（含），奥氮平呈线性增加，然后到第28天下降。结论是，通过渗透性微型泵给药奥氮平在动物模型中是可行的，以反映人体内发生的情况，尽管间隔应限制为2周。同样，讨论了溶解奥氮平以减少氧化的策略。

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