Campbell R R, Hasinoff B, Chernenko G, Barrowman J, Campbell N R
Department of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Can J Physiol Pharmacol. 1990 May;68(5):603-7. doi: 10.1139/y90-087.
Ferrous sulfate decreases L-dopa bioavailability in humans probably as a result of binding of L-dopa by iron in the gastrointestinal tract. This study was conducted to determine if iron by binding L-dopa decreases L-dopa absorption and to investigate the effect of different pH buffers on intestinal absorption of L-dopa in the presence and absence of ferrous sulfate. A rat model developed to examine drug absorption was used. Control animals had buffered [14C]L-dopa solutions injected into two in vivo closed segments of intestine; a 5-cm duodenal and a 5-cm proximal jejunal segment. These studies were conducted using solutions buffered at pH 5.5, 6.5, 7.5, and 8.5. An identical procedure was followed for experimental animals except ferrous sulfate was injected with the buffered L-dopa solutions. Ferrous sulfate resulted in a reduction in L-dopa absorption in the buffers at all pHs in both the duodenum and jejunum. The average reduction in L-dopa absorption in the presence of iron was 22.6% in the duodenum and 23.9% in the jejunum. There was a tendency for ferrous sulfate to cause a greater reduction in L-dopa absorption as the buffer pH increased. There was also a decrease in L-dopa absorption in the higher pH buffers in the absence of iron. Despite this latter result, in the jejunum there was an increase in the percent reduction in L-dopa absorption associated with ferrous sulfate as pH increased. Although this tendency was not as consistent in the duodenum as the jejunum, the combined results are compatible with the chemical model of increased L-dopa--iron binding as pH increases.
硫酸亚铁可能通过铁在胃肠道中与左旋多巴结合而降低人体中左旋多巴的生物利用度。本研究旨在确定铁与左旋多巴结合是否会降低左旋多巴的吸收，并研究在有无硫酸亚铁的情况下不同pH缓冲液对左旋多巴肠道吸收的影响。使用了一种用于检查药物吸收的大鼠模型。对照动物将缓冲的[14C]左旋多巴溶液注入两段体内封闭的肠道；一段5厘米长的十二指肠段和一段5厘米长的空肠近端段。这些研究使用pH值为5.5、6.5、7.5和8.5的缓冲溶液进行。实验动物采用相同的程序，只是将硫酸亚铁与缓冲的左旋多巴溶液一起注射。硫酸亚铁导致十二指肠和空肠中所有pH值缓冲液中左旋多巴的吸收减少。在有铁存在的情况下，十二指肠中左旋多巴吸收的平均减少率为22.6%，空肠中为23.9%。随着缓冲液pH值的升高，硫酸亚铁有使左旋多巴吸收减少更多的趋势。在没有铁的情况下，较高pH缓冲液中左旋多巴的吸收也会减少。尽管有后一个结果，但在空肠中，随着pH值升高，与硫酸亚铁相关的左旋多巴吸收减少百分比增加。虽然这种趋势在十二指肠中不如在空肠中一致，但综合结果与随着pH值升高左旋多巴-铁结合增加的化学模型相符。
