Ogiso T, Iwaki M, Tanino T, Kawafuchi R, Hata S
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Biol Pharm Bull. 1994 Jan;17(1):112-6. doi: 10.1248/bpb.17.112.
To better define the mechanism of the increased plasma concentration of propranolol (PL) after meals, the effect of the dietary constitution of a meal on the kinetics of PL and beta-naphthoxylactic acid (NLA), a main metabolite, after administration of the drug, was investigated in rats. Additionally, the hepatic uptake of PL and cytochrome P-450 (P-450) content and uridine 5'-diphosphoglucuronyltransferase (UDPGT) activity in liver were measured after glucose intake. As a result, protein (skim milk) intake slightly, but not significantly, increased the area under the plasma concentration-time curve (AUC) and bioavailability of PL, with a slight increase (16%) in hepatic blood flow, and enhanced PL metabolism to NLA. Soybean oil and fatty acid intake significantly decreased the bioavailability of PL, while glucose intake dramatically decreased the hepatic uptake of PL and P-450 content at high glucose levels, resulting in a decrease in the plasma PL concentration at the initial time period and in the inhibition of a metabolic conversion to NLA. Thus, a possible mechanism involved in the effect of food on PL bioavailability could have been due largely to the decreased microsomal P-450 content and hepatic uptake of PL after glucose intake, but only partly to the increased hepatic blood flow after protein intake.
为了更好地确定餐后普萘洛尔（PL）血浆浓度升高的机制，研究了大鼠进食后膳食组成对给药后PL及主要代谢产物β-萘氧基乳酸（NLA）动力学的影响。此外，还测定了摄入葡萄糖后肝脏对PL的摄取、细胞色素P-450（P-450）含量以及肝脏中尿苷5'-二磷酸葡萄糖醛酸基转移酶（UDPGT）的活性。结果显示，摄入蛋白质（脱脂牛奶）使PL的血浆浓度-时间曲线下面积（AUC）和生物利用度略有增加，但不显著，肝血流量略有增加（16%），并增强了PL向NLA的代谢。摄入大豆油和脂肪酸显著降低了PL的生物利用度，而摄入葡萄糖在高糖水平时显著降低了肝脏对PL的摄取和P-450含量，导致初始时间段血浆PL浓度降低，并抑制了向NLA的代谢转化。因此，食物对PL生物利用度影响的一种可能机制很大程度上可能是由于摄入葡萄糖后微粒体P-450含量降低和肝脏对PL的摄取减少，但部分原因是摄入蛋白质后肝血流量增加。
