来自缓释烟酸制剂的烟酸及其代谢物的血浆和尿液药代动力学。

Plasma and urine pharmacokinetics of niacin and its metabolites from an extended-release niacin formulation.

作者信息

Menon R M, Adams M H, González M A, Tolbert D S, Leu J H, Cefali E A

机构信息

Kos Pharmaceuticals, Weston, FL 33326, USA.

出版信息

Int J Clin Pharmacol Ther. 2007 Aug;45(8):448-54. doi: 10.5414/cpp45448.

DOI:10.5414/cpp45448

PMID:17725178

Abstract

OBJECTIVE

To characterize plasma and urine pharmacokinetics of niacin and its metabolites after oral administration of 2,000 mg of extended-release (ER) niacin in healthy male volunteers.

METHODS

Niacin ER was administered to 12 healthy male subjects following a low-fat snack. Plasma was collected for 12 h post dose and was analyzed for niacin, nicotinuric acid (NUA), nicotinamide (NAM) and nicotinamide-N-oxide (NNO). Urine was collected for 96 h post dose and analyzed for niacin and its metabolites, NUA, NAM, NNO, N-methylnicotinamide (MNA) and N-methyl-2-pyridone-5-carboxamide (2PY).

RESULTS

Mean niacin Cmax and AUC(0-t) values were 9.3 microg/ml and 26.2 microg x h/ml and were the highest of all analytes measured. Peak niacin and NUA levels occurred at 4.6 h (median) while tmax for NAM and NNO were 8.6 and 11.1 h, respectively. The mean plasma terminal half-life for niacin (0.9 h) and NUA (1.3 h) was shorter as compared to NAM (4.3 h). Urine recovery of niacin and metabolites accounted for 69.5% of the administered dose; only 3.2% was excreted as niacin. The highest recovery was for 2PY (37.9%), followed by MNA (16.0%) and NUA (11.6%). Mean half-lives for 2PY and MNA calculated in urine were 12.6 and 12.8 h, respectively.

CONCLUSIONS

Niacin was extensively metabolized following oral administration, and about 70% of the administered dose is recovered in urine in 96 h as niacin, NUA, MNA, NNO, NAM and 2PY. The plasma levels of the parent niacin were higher than its metabolites though only about 3% of the unchanged drug is recovered in urine.

摘要

目的

在健康男性志愿者口服2000毫克缓释烟酸后，对烟酸及其代谢产物的血浆和尿液药代动力学进行表征。

方法

在低脂小吃后，向12名健康男性受试者给予缓释烟酸。给药后12小时收集血浆，分析其中的烟酸、烟尿酸（NUA）、烟酰胺（NAM）和烟酰胺 - N - 氧化物（NNO）。给药后96小时收集尿液，分析其中的烟酸及其代谢产物，包括NUA、NAM、NNO、N - 甲基烟酰胺（MNA）和N - 甲基 - 2 - 吡啶酮 - 5 - 羧酰胺（2PY）。

结果

烟酸的平均Cmax和AUC(0 - t)值分别为9.3微克/毫升和26.2微克·小时/毫升，在所有测量的分析物中最高。烟酸和NUA的峰值水平出现在4.6小时（中位数），而NAM和NNO的tmax分别为8.6小时和11.1小时。与NAM（4.3小时）相比，烟酸（0.9小时）和NUA（1.3小时）的平均血浆终末半衰期较短。烟酸及其代谢产物的尿液回收率占给药剂量的69.5%；仅3.2%以烟酸形式排泄。回收率最高的是2PY（37.9%），其次是MNA（16.0%）和NUA（11.6%）。尿液中计算出的2PY和MNA的平均半衰期分别为12.6小时和12.8小时。