el-Shattawy H H, el-Sherbiny A I, Bayomi M A, Abdel-Fatah I M
Dept. of Pharmaceutics, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Eur J Drug Metab Pharmacokinet. 1991;Spec No 3:397-405.
The interaction of the anti-inflammatory drug, piroxicam, with some naturally occurring polymers-viz gamma-globulin, bovine serum-albumin, bovine synovial fluid and casein was characterized in this study. This was done using equilibrium dialysis method where the dialysis membrane was permeable only to the drug molecules while polymers and formed complex(es) cannot pass through. The amount of permeable piroxicam molecules was determined spectrophotometrically. It was found out that increasing the concentration of piroxicam was accompanied by an increase in the amount of piroxicam bound to the investigated natural polymers. The maximum binding capacity of the investigated polymers for the drug as revealed by Langmuir plots, could be arranged in ascending manner as follows: synovial fluid, albumin, casein and gamma-globulin. The binding parameters K (association constant) and n (the number of binding sites available on the polymer) were determined using Sandberg plots. It was found that two classed of binding sites were involved in the interaction of piroxicam with gamma-globulin, albumin and casein. Increasing salt concentration was accompanied by a decrease in piroxicam binding with the investigated polymers till a constant value of ionic strength (0.6 mole/liter). This result may suggest the ionic nature in binding of piroxicam with the investigated polymers. It was concluded that piroxicam is strongly bound to the investigated natural polymers with different degree of binding, such binding may affect the pharmacological effect of piroxicam. An in-vivo absorption study was performed on eight male healthy volunteers to compare the bioavailability of piroxicam in presence and absence of casein using plasma data after 100 mg single dose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究对消炎药物吡罗昔康与一些天然存在的聚合物（即γ-球蛋白、牛血清白蛋白、牛滑液和酪蛋白）之间的相互作用进行了表征。这是通过平衡透析法完成的，在该方法中，透析膜仅对药物分子具有渗透性，而聚合物和形成的复合物不能通过。通过分光光度法测定可渗透的吡罗昔康分子的量。结果发现，随着吡罗昔康浓度的增加，与所研究的天然聚合物结合的吡罗昔康量也增加。根据朗缪尔图显示，所研究的聚合物对该药物的最大结合能力可按如下升序排列：滑液、白蛋白、酪蛋白和γ-球蛋白。使用桑德伯格图确定结合参数K（缔合常数）和n（聚合物上可用的结合位点数）。发现吡罗昔康与γ-球蛋白、白蛋白和酪蛋白的相互作用涉及两类结合位点。盐浓度增加伴随着吡罗昔康与所研究聚合物的结合减少，直至离子强度达到恒定值（0.6摩尔/升）。该结果可能表明吡罗昔康与所研究聚合物结合的离子性质。得出的结论是，吡罗昔康与所研究的天然聚合物以不同程度紧密结合，这种结合可能会影响吡罗昔康的药理作用。对八名健康男性志愿者进行了体内吸收研究，以比较在单剂量100毫克治疗后，存在和不存在酪蛋白时吡罗昔康的生物利用度，并使用血浆数据进行比较。（摘要截选至250字）
