Garcia Juan J, Fernandez Nelida, Carriedo Demetrio, Diez M Jose, Sahagun Ana, Gonzalez Aranzazu, Calle Angela, Sierra Matilde
Area de Farmacologia, Universidad de Leon, 24071 Leon, Spain.
Eur Neuropsychopharmacol. 2005 Oct;15(5):497-503. doi: 10.1016/j.euroneuro.2005.01.005. Epub 2005 Mar 23.
Fiber therapy could be used in patients with Parkinson disease to reduce the symptoms of gastrointestinal disorders; however, it could interact with levodopa reducing its effectiveness. In this experimental study we have investigated whether the presence of Plantago ovata husk (water-soluble fiber) modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route at the same time. We have also studied whether pharmacokinetic modifications are fiber-dose dependent (100 and 400 mg/kg). The extent of levodopa absorbed when administering 100 mg/kg of fiber (AUC=43.4 mug min ml(-1)) is approximately the same as when levodopa is administered alone (AUC=47.1 microg min ml(-1)); however, Cmax is lower (1.04 versus 1.43 microg ml(-1)). Results obtained indicate that fiber at the higher dose increases the extent of levodopa absorbed (AUC=62.2 microg min ml(-1)), being the value of Cmax similar (1.46 microg ml(-1)). The value of tmax increases from 10 min when levodopa is administered alone to 20 min when the animals receive fiber. On the other hand, since certain time on, levodopa concentrations are always higher in the groups that receive fiber: 60 min with 100 mg/kg fiber and 20 min with 400 mg/kg fiber. Fiber also increases the mean residence time (MRT). P. ovata husk administration with levodopa could be beneficial, not only in patients with constipation, due to: lower adverse reactions (lower values of Cmax) and longer and more stable effects (higher final concentrations and more time in the body).
纤维疗法可用于帕金森病患者,以减轻胃肠道紊乱症状;然而,它可能与左旋多巴相互作用,降低其疗效。在本实验研究中,我们调查了车前草壳(水溶性纤维)的存在是否会改变家兔口服20mg/kg左旋多巴时的生物利用度和其他药代动力学参数。我们还研究了药代动力学改变是否与纤维剂量有关(100mg/kg和400mg/kg)。给予100mg/kg纤维时左旋多巴的吸收程度(AUC = 43.4μg·min·ml⁻¹)与单独给予左旋多巴时(AUC = 47.1μg·min·ml⁻¹)大致相同;然而,Cmax较低(分别为1.04和1.43μg·ml⁻¹)。所得结果表明,高剂量纤维会增加左旋多巴的吸收程度(AUC = 62.2μg·min·ml⁻¹),Cmax值相似(1.46μg·ml⁻¹)。tmax值从单独给予左旋多巴时的10分钟增加到动物接受纤维时的20分钟。另一方面,从某一时刻起,接受纤维的组中左旋多巴浓度始终较高:给予100mg/kg纤维时为60分钟,给予400mg/kg纤维时为20分钟。纤维还会增加平均驻留时间(MRT)。将车前草壳与左旋多巴一起给药可能有益,不仅对便秘患者有益,原因在于:不良反应较少(Cmax值较低),效果更持久且更稳定(最终浓度较高且在体内停留时间更长)。