Shiba T, Kajinuma H, Suzuki K, Hagura R, Kawai A, Katagiri H, Sando H, Shirakawa W, Kosaka K, Kuzuya N
Diabetes Res Clin Pract. 1986 Sep-Oct;2(5):301-6. doi: 10.1016/s0168-8227(86)80007-9.
Serum levels of gliclazide were determined by radioimmunoassay in seven healthy controls and in 18 diabetic in-patients receiving single oral dosing and consecutive dosing over 5 days. Following a single oral dose of 40 mg in the seven controls and eight diabetic patients, and 120 mg in ten diabetic patients, the serum levels of gliclazide peaked on average at 2 h, followed by a slow decline, the t1/2 being 16.5 h in the volunteers, 12.3 h in the diabetic patients receiving 40 mg, and 10.5 h in those receiving 120 mg. During consecutive administration, the serum levels both at fasting and at the peak reached a plateau in 2 days and no further accumulations were observed. The steady-state peak levels of gliclazide in the diabetic patients revealed a strongly positive correlation with the dose per m2 body surface area (r = 0.78, P less than 0.001), and their steady-state fasting levels correlated positively but weakly with the dose per m2 body surface area (r = 0.48, P less than 0.05). Thus, measuring either the fasting or the peak concentration of gliclazide will be useful for monitoring drug concentration in the serum. Pharmacokinetics of gliclazide will contribute to the elucidation of the relationship of serum level and clinical effectiveness in diabetic subjects.
采用放射免疫分析法测定了7名健康对照者以及18名接受单次口服给药和连续5天给药的糖尿病住院患者血清中的格列齐特水平。在7名对照者和8名糖尿病患者中单次口服40mg，在10名糖尿病患者中单次口服120mg后，格列齐特血清水平平均在2小时达到峰值，随后缓慢下降，志愿者的t1/2为16.5小时，接受40mg的糖尿病患者为12.3小时，接受120mg的患者为10.5小时。在连续给药期间，空腹和峰值时的血清水平在2天内达到平稳状态，未观察到进一步蓄积。糖尿病患者中格列齐特的稳态峰值水平与每平方米体表面积的剂量呈强正相关（r = 0.78，P<0.001），其稳态空腹水平与每平方米体表面积的剂量呈正相关但较弱（r = 0.48，P<0.05）。因此，测定格列齐特的空腹或峰值浓度对于监测血清中的药物浓度将是有用的。格列齐特的药代动力学将有助于阐明糖尿病患者血清水平与临床疗效之间的关系。
