Lehmann D F, Holohan P D, Blair D C
Department of Medicine, State University of New York Health Science Center at Syracuse, USA.
J Clin Pharmacol. 1996 Dec;36(12):1149-53. doi: 10.1002/j.1552-4604.1996.tb04169.x.
Hypersensitivity reactions to trimethoprim/sulfamethoxazole occur with a high frequency in human immunodeficiency virus (HIV)-infected patients. This study tested whether differences in oxidative metabolism and plasma reductive capacity correlate with sulfonamide intolerance in patients with HIV. Eighteen stable outpatients with HIV were prospectively studied. Nine patients had documented histories of hypersensitivity reactions to trimethoprim/sulfamethoxazole and nine did not. Urinary caffeine metabolite ratios assessed the activity of two oxidative enzymatic pathways: cytochrome P-450 1A2 (demethylation) and 8-hydroxylation. Plasma cyst(e)ine was used as a measure of reductive capacity. The trimethoprim/sulfamethoxazole-intolerant group showed greater rates of 8-hydroxylation, lower rates of demethylation, and lower cyst(e)ine levels. The results of this pilot study extend previous observations of differences in oxidative metabolism and reductive capacity that exist within the population of HIV-infected individuals. In addition, these findings lay the groundwork for future interventional studies that could use agents to inhibit sulfonamide oxidation and increase reductive capacity in sulfonamide-intolerant patients with HIV when rechallenged with trimethoprim/sulfamethoxazole.
对甲氧苄啶/磺胺甲恶唑的超敏反应在人类免疫缺陷病毒（HIV）感染患者中频繁发生。本研究测试了氧化代谢和血浆还原能力的差异是否与HIV患者的磺胺类药物不耐受相关。对18名病情稳定的HIV门诊患者进行了前瞻性研究。9名患者有对甲氧苄啶/磺胺甲恶唑超敏反应的记录病史，9名患者没有。尿咖啡因代谢物比率评估了两种氧化酶途径的活性：细胞色素P - 450 1A2（去甲基化）和8 - 羟基化。血浆胱氨酸用作还原能力的指标。甲氧苄啶/磺胺甲恶唑不耐受组表现出更高的8 - 羟基化率、更低的去甲基化率和更低的胱氨酸水平。这项初步研究的结果扩展了先前对HIV感染人群中存在的氧化代谢和还原能力差异的观察。此外，这些发现为未来的干预性研究奠定了基础，这些研究可以使用药物抑制磺胺类药物氧化，并在对甲氧苄啶/磺胺甲恶唑再次激发试验时增加HIV磺胺类药物不耐受患者的还原能力。
