Albengres E, Urien S, Barre J, Nguyen P, Bree F, Jolliet P, Tillement J P, Tsai R S, Carrupt P A, Testa B
Centre Régional de Pharmacovigilance de Paris--Val de Marne, Centre Hospitalier Intercommunal, Créteil, France.
Int J Tissue React. 1993;15(3):125-34.
Six oxicams, sudoxicam, isoxicam, piroxicam, tenoxicam, meloxicam and lornoxicam, were compared in an attempt to understand why, despite close chemical structures, two of them were associated with an increased risk of toxicity in patients. Different factors have been revealed which may explain these differences. A weak association constant to human serum albumin (HSA), together with a high plasma concentration, favours a rapid increase in unbound concentration (Cu) when total plasma concentration rises (peak of absorption). Pathological states may enhance this increase when both HSA plasma concentration is decreased and free fatty acid concentrations are increased. However, the main cause of toxicity may be the existence in some subjects of HSA natural mutants whose ability to bind oxicams is markedly lower than normal.
对六种昔康类药物，即舒多昔康、异昔康、吡罗昔康、替诺昔康、美洛昔康和氯诺昔康进行了比较，以试图弄清楚为什么尽管它们的化学结构相近，但其中两种药物与患者中毒风险增加有关。已经揭示了不同的因素，这些因素可能解释这些差异。与人类血清白蛋白（HSA）的结合常数较弱，再加上血浆浓度较高，当总血浆浓度升高（吸收峰值）时，有利于未结合浓度（Cu）迅速增加。当HSA血浆浓度降低且游离脂肪酸浓度增加时，病理状态可能会加剧这种增加。然而，中毒的主要原因可能是某些受试者存在HSA天然突变体，其结合昔康类药物的能力明显低于正常水平。
