Petersen E N, Bechgaard E, Sortwell R J, Wetterberg L
Eur J Pharmacol. 1978 Nov 1;52(1):115-9. doi: 10.1016/0014-2999(78)90028-6.
The potent 5-hydroxytryptamine (5HT) uptake inhibitor FG 7051 (paroxetine, INN) was administered to rhesus monkeys in doses of 1.0, 2.5 or 7.5 mg/kg by oral gavage once daily for 13 weeks. Blood samples for analysis of 5HT in whole blood and paroxetine in plasma were taken prior to and after 1, 4 and 13 weeks of treatment. The lowest dose 1 mg/kg caused 30% depletion of 5HT in whole blood with a level of paroxetine in plasma below 2 ng/ml. Doses of 2.5 mg/kg produced an 85% depletion of 5HT and a steady state plasma concentration of about 5 ng paroxetine/ml, while 7.5 mg/kg caused a 93% depletion of 5HT and a steady state plasma concentration of 100--450 ng paroxetine/ml. There was no concentration-dependent 5HT reduction with the highest dose level suggesting that maximal depletion was produced by concentrations below 100 ng/ml. The results showed that paroxetine is a strong depletor of 5HT from whole blood of monkeys conceivably because it inhibits 5HT uptake inhibition. The effect of the drug reached its maximum within 1 week and no tolerance developed during 13 weeks.
强效5-羟色胺（5HT）摄取抑制剂FG 7051（帕罗西汀，国际非专利药品名称）以1.0、2.5或7.5mg/kg的剂量通过口服灌胃给予恒河猴，每日一次，持续13周。在治疗1、4和13周之前和之后采集血样，用于分析全血中的5HT和血浆中的帕罗西汀。最低剂量1mg/kg导致全血中5HT耗竭30%，血浆中帕罗西汀水平低于2ng/ml。2.5mg/kg的剂量使5HT耗竭85%，血浆中帕罗西汀稳态浓度约为5ng/ml，而7.5mg/kg导致5HT耗竭93%，血浆中帕罗西汀稳态浓度为100 - 450ng/ml。最高剂量水平下不存在浓度依赖性5HT降低，这表明浓度低于100ng/ml时产生了最大耗竭。结果表明，帕罗西汀是猴子全血中5HT的强效耗竭剂，可能是因为它抑制5HT摄取。药物作用在1周内达到最大值，并且在13周内未产生耐受性。
