Division of Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Pharmacol Ther. 2011 Nov;132(2):158-69. doi: 10.1016/j.pharmthera.2011.06.001. Epub 2011 Jun 16.
The acute porphyrias are a group of disorders which result from inherited defects in the enzymes of the heme biosynthetic pathway. Affected patients are prone to potentially fatal acute attacks. These attacks are frequently precipitated by exposure to commonly used drugs. Correctly identifying the safety or otherwise of drugs in porphyria is therefore important. In this review we describe how clinical experience and the findings of experimental systems using whole animal or cell culture models have been interpreted to determine porphyrogenicity, that is the potential of a drug to induce an acute attack in a patient carrying a gene for acute porphyria. It is now well established that induction of delta-aminolevulinic acid synthase, the rate controlling enzyme of the heme biosynthetic pathway, is fundamental to porphyrogenicity, and that drug-induced hepatic heme depletion via induction or suicidal inactivation of cytochrome P450 is central to this process. The process is now sufficiently well understood that prediction of porphyrogenicity from structural and functional information alone would appear to be justified.
急性卟啉症是一组由于血红素生物合成途径中酶的遗传缺陷引起的疾病。受影响的患者容易发生潜在致命的急性发作。这些发作通常由常用药物的暴露引发。因此，正确识别卟啉症患者的药物安全性非常重要。在这篇综述中，我们描述了如何解释临床经验和使用全动物或细胞培养模型的实验系统的发现，以确定药物的致卟啉性，即药物在携带急性卟啉症基因的患者中引发急性发作的潜力。现在已经确立，δ-氨基酮戊酸合酶（血红素生物合成途径的限速酶）的诱导是致卟啉性的基础，而通过细胞色素 P450 的诱导或自杀失活导致肝血红素耗竭是这一过程的核心。这个过程现在已经被充分理解，因此似乎可以仅从结构和功能信息来预测致卟啉性。
