Persiani S, Rocchetti M, Pacciarini M A, Holt B, Toon S, Strolin-Benedetti M
Department of Pharmacokinetics and Metabolism, Pharmacia S.p.A., Nerviano (MI), Italy.
Biopharm Drug Dispos. 1996 Jul;17(5):443-55. doi: 10.1002/(SICI)1099-081X(199607)17:5<443::AID-BDD443>3.0.CO;2-U.
The effect of food on the pharmacokinetics and tolerability of cabergoline in man was investigated. For this purpose an open, randomized, single-dose study was conducted in 12 healthy male volunteers who received 1 mg cabergoline as tablets both under fasting conditions and after a breakfast containing a substantial amount of carbohydrates, fat, and proteins, in a crossover fashion. The two treatments were separated by a 4 week washout period. Plasma and urine were collected up to 336 and 168 h respectively after administration and cabergoline concentration was measured in both fluids using a validated radioimmunoassay. Tolerability assessment included haematology, blood chemistry, and urinalysis, blood pressure and heart rate measurements, and ECG. Under both fasting and fed conditions low but persistent cabergoline plasma levels were observed in the present study up to 2 weeks after drug intake, in agreement with the long-lasting prolactin-lowering activity of the drug. In subjects receiving cabergoline under fed or fasting conditions, Cmax values averaged 44 and 54 pg mL(-1), AUC(0-336 h) averaged 6392 and 5331 pg h mL(-1), Ae(0-168 h) averaged 12.7 and 11.9 micrograms, and t1/2 averaged 109.7 and 101.3 h, respectively. No statistically significant difference was found when Cmax, AUC(0-336 h), t1/2, and Ae(0-168 h) from subjects treated under fasting and fed conditions were compared. Median tmax values in subjects treated under fasting or fed conditions were identical (2.5 h). The statistical analysis applied to the parameters chosen to evaluate the variations in the blood pressure profiles observed either supine or standing did not show any significant difference between the fed and fasting conditions. Heart rate values were not significantly modified after cabergoline under either fed or fasting conditions. Laboratory evaluation showed some minor deviations from normal, which were not clinically relevant (only one subject showed an occasional and transient elevation in alkaline phosphatase which disappeared in the subsequent laboratory evaluations) and were considered for the most part not to be drug related. Eleven subjects reported adverse events (one after both treatments, five only after drug intake under fasting conditions, and five only after drug intake with food.
研究了食物对卡麦角林在人体药代动力学和耐受性的影响。为此，对12名健康男性志愿者进行了一项开放、随机、单剂量研究，这些志愿者以交叉方式在禁食条件下和食用含有大量碳水化合物、脂肪和蛋白质的早餐后均接受1mg卡麦角林片剂。两种治疗之间间隔4周的洗脱期。给药后分别收集血浆和尿液长达336小时和168小时，并使用经过验证的放射免疫分析法测定两种体液中的卡麦角林浓度。耐受性评估包括血液学、血液化学、尿液分析、血压和心率测量以及心电图。在本研究中，在禁食和进食条件下，在药物摄入后长达2周均观察到较低但持续的卡麦角林血浆水平，这与该药物持久的降低催乳素活性一致。在进食或禁食条件下接受卡麦角林的受试者中，Cmax值平均分别为44和54pg mL(-1)，AUC(0 - 336h)平均分别为6392和5331pg h mL(-1)，Ae(0 - 168h)平均分别为12.7和11.9微克，t1/2平均分别为109.7和101.3小时。比较禁食和进食条件下治疗的受试者的Cmax、AUC(0 - 336h)、t1/2和Ae(0 - 168h)时，未发现统计学上的显著差异。禁食或进食条件下治疗的受试者的中位tmax值相同(2.5小时)。对用于评估仰卧或站立时观察到的血压变化情况的参数进行的统计分析未显示进食和禁食条件之间有任何显著差异。在进食或禁食条件下，卡麦角林给药后心率值均未显著改变。实验室评估显示有一些与正常情况的轻微偏差，这些偏差无临床相关性(只有一名受试者偶尔出现碱性磷酸酶短暂升高，在随后的实验室评估中消失)，并且在很大程度上被认为与药物无关。11名受试者报告了不良事件(一名受试者在两种治疗后均出现，五名受试者仅在禁食条件下服药后出现，五名受试者仅在进食时服药后出现)。
