Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Azenha 90610-000 Porto Alegre,Rio Grande do Sul, Brazil.
Ther Drug Monit. 2012 Oct;34(5):545-53. doi: 10.1097/FTD.0b013e318263c6c5.
Fenproporex hydrochloride (FEN) is an anorectic drug used in the treatment of obesity, and its major metabolite is amphetamine (AMP), another central nervous system stimulant. The concentration versus time profile of FEN and its metabolite AMP has been described in classic biological matrices such as plasma and urine; however, there are no reports of such data in oral fluid.
The aim of this study is to describe the pharmacokinetics of FEN and AMP in oral fluid after intake of FEN.
Twenty-five milligrams of FEN (1 capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral fluid samples were collected with a Quantisal device during 24.00 hours after drug ingestion. These samples were submitted to solid-phase microextraction before analysis by gas chromatography-mass spectrometry in the selected-ion-monitoring mode, using deuterium-labeled AMP as internal standard.
After FEN administration, both analytes could be detected in oral fluid of all volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN peak concentrations occurred between 1.00 and 1.50 hours after administration and were between 70.7 and 227.5 μg/L. For AMP, peak concentration occurred between 1.50 and 4.00 hours, reaching 33.0-150.9 μg/L.
The authors observed that oral administration of FEN resulted in significant amounts of FEN and AMP in oral fluid, showing that oral fluid could be a biological matrix suitable for pharmacokinetic studies for both analytes. Using a compartmental approach, FEN data were best fitted by 1-compartment model with first-order input and output, whereas AMP followed a 2-compartment model with first-order input and output.
盐酸芬氟拉明（FEN）是一种用于治疗肥胖症的食欲抑制剂，其主要代谢物是苯丙胺（AMP），另一种中枢神经系统兴奋剂。FEN 和其代谢物 AMP 的浓度-时间曲线已在经典的生物基质中描述，如血浆和尿液；然而，在口腔液中尚无此类数据的报道。
本研究旨在描述口服 FEN 后口腔液中 FEN 和 AMP 的药代动力学。
6 名男性志愿者口服 25 毫克 FEN（1 粒 Desobesi-m），在药物摄入后 24.00 小时内使用 Quantisal 设备采集口腔液样本。这些样本在进行气相色谱-质谱分析前，使用氘代 AMP 作为内标，通过固相微萃取进行预处理，采用选择离子监测模式。
在 FEN 给药后，所有志愿者的口腔液中均能检测到两种分析物，初始检测时间从 0.50 到 1.00 小时不等。FEN 的峰值浓度出现在给药后 1.00 至 1.50 小时之间，浓度范围为 70.7 至 227.5 μg/L。对于 AMP，峰值浓度出现在 1.50 至 4.00 小时之间，达到 33.0-150.9 μg/L。
作者观察到，FEN 的口服给药导致口腔液中存在大量的 FEN 和 AMP，表明口腔液可能是适用于两种分析物药代动力学研究的生物基质。使用房室模型方法，FEN 数据最佳拟合为 1 房室模型，具有一级输入和输出，而 AMP 则遵循一级输入和输出的 2 房室模型。
