Martin Paul D, Warwick Mike J, Dane Aaron L, Hill Steve J, Giles Petrina B, Phillips Paul J, Lenz Eva
AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom.
Clin Ther. 2003 Nov;25(11):2822-35. doi: 10.1016/s0149-2918(03)80336-3.
Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitor, or statin, that has been developed for the treatment of dyslipidemia.
This study assessed the metabolism, excretion, and pharmacokinetics of a single oral dose of radiolabeled rosuvastatin ([14C]-rosuvastatin) in healthy volunteers.
This was a nonrandomized, open-label, single-day trial. Healthy adult male volunteers were given a single oral dose of [14C]-rosuvastatin 20 mg (20 mL [14C]-rosuvastatin solution, nominally containing 50 microCi radioactivity). Blood, urine, and fecal samples were collected up to 10 days after dosing. Tolerability assessments were made up to 10 days after dosing (trial completion) and at a follow-up visit within 14 days of trial completion.
Six white male volunteers aged 36 to 52 years (mean, 43.7 years) participated in the trial. The geometric mean peak plasma concentration (C(max)) of rosuvastatin was 6.06 ng/mL and was reached at a median of 5 hours after dosing. At C(max), rosuvastatin accounted for approximately 50% of the circulating radioactive material. Approximately 90% of the rosuvastatin dose was recovered in feces, with the remainder recovered in urine. The majority of the dose (approximately 70%) was recovered within 72 hours after dosing; excretion was complete by 10 days after dosing. Metabolite profiles in feces indicated that rosuvastatin was excreted largely unchanged (76.8% of the dose). Two metabolites-rosuvastatin-5S-lactone and N-desmethyl rosuvastatin-were present in excreta. [14C]-rosuvastatin was well tolerated; 2 volunteers reported 4 mild adverse events that resolved without treatment.
The majority of the rosuvastatin dose was excreted unchanged. Given the absolute bioavailability (20%) and estimated absorption (approximately 50%) of rosuvastatin, this finding suggests that metabolism is a minor route of clearance for this agent.
瑞舒伐他汀是一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，即他汀类药物，已被开发用于治疗血脂异常。
本研究评估了健康志愿者单次口服放射性标记瑞舒伐他汀（[14C] - 瑞舒伐他汀）后的代谢、排泄及药代动力学情况。
这是一项非随机、开放标签的单日试验。健康成年男性志愿者单次口服20毫克[14C] - 瑞舒伐他汀（20毫升[14C] - 瑞舒伐他汀溶液，标称含有50微居里放射性）。给药后长达10天收集血液、尿液和粪便样本。给药后长达10天（试验结束）以及试验结束后14天内的随访时进行耐受性评估。
6名年龄在36至52岁（平均43.7岁）的白人男性志愿者参与了试验。瑞舒伐他汀的几何平均血浆峰浓度（C(max)）为6.06纳克/毫升，给药后中位数5小时达到。在C(max)时，瑞舒伐他汀约占循环放射性物质的50%。约90%的瑞舒伐他汀剂量在粪便中回收，其余在尿液中回收。大部分剂量（约70%）在给药后72小时内回收；给药后10天排泄完毕。粪便中的代谢物谱表明，瑞舒伐他汀大部分以原形排泄（占剂量的76.8%）。排泄物中存在两种代谢物——瑞舒伐他汀-5S-内酯和N-去甲基瑞舒伐他汀。[14C] - 瑞舒伐他汀耐受性良好；2名志愿者报告了4起轻度不良事件，未经治疗即缓解。
大部分瑞舒伐他汀剂量以原形排泄。鉴于瑞舒伐他汀的绝对生物利用度（20%）和估计吸收率（约5），这一发现表明代谢是该药物清除的次要途径。
