Dr. Falk Pharma GmbH, Freiburg, Germany.
Digestion. 2013;87(2):110-7. doi: 10.1159/000346403. Epub 2013 Jan 25.
BACKGROUND/AIMS: Topically administered glucocorticoids such as budesonide have the potential of being established as first-line medical treatment of eosinophilic esophagitis (EoE). Safety of budesonide is based on high elimination by cytochrome P450 3A (CYP3A) enzymes. We aimed to investigate systemic absorption and elimination of a new budesonide formulation in patients with active EoE in comparison with healthy controls.
After single and multiple doses of orodispersible budesonide (4 mg/day) the parent drug, its CYP3A-dependent metabolites, and endogenous cortisol were determined in 12 adult patients with active EoE and 12 healthy controls. An approved ileal-release formulation of budesonide was taken for reference. Molar ratios of metabolite formation in plasma were used as indices of CYP3A metabolic function.
CYP3A-dependent metabolite formation was significantly reduced in patients with active EoE as compared to healthy controls. Impaired biotransformation was reflected by a significantly higher extent of budesonide absorption and elongated elimination half-life in EoE patients. Comparison of morning serum cortisol levels at baseline with those after 1 week of treatment with budesonide revealed a significant decrease in EoE patients but not in healthy subjects.
Active EoE is associated with reduced elimination of budesonide via CYP3A, the major subfamily of drug-metabolizing enzymes in humans.
背景/目的：局部给予布地奈德等糖皮质激素有可能成为嗜酸性食管炎（EoE）的一线治疗方法。布地奈德的安全性基于细胞色素 P450 3A（CYP3A）酶的高消除率。我们旨在研究新型布地奈德制剂在活动性 EoE 患者中的全身吸收和消除情况，并与健康对照组进行比较。
在 12 例活动性 EoE 患者和 12 例健康对照者中，分别单次和多次给予口腔崩解布地奈德（4mg/天）后，测定母体药物、其 CYP3A 依赖性代谢物和内源性皮质醇。以批准的回肠释放型布地奈德制剂作为参考。血浆中代谢产物形成的摩尔比作为 CYP3A 代谢功能的指标。
与健康对照组相比，活动性 EoE 患者的 CYP3A 依赖性代谢产物形成明显减少。EoE 患者的生物转化受损，表现为布地奈德吸收程度显著增加，消除半衰期延长。与布地奈德治疗前的早晨血清皮质醇水平相比，EoE 患者在治疗 1 周后明显下降，但健康受试者则没有。
活动性 EoE 患者的 CYP3A 代谢能力下降，导致布地奈德的消除减少，CYP3A 是人类药物代谢酶的主要亚家族。
