Ross R J M, Jabbar A, Jones T H, Roberts B, Dunkley K, Hall J, Long A, Levine H, Cullen D R
Department of Endocrinology, Sheffield Teaching Hospitals, Sheffield S5 7AU, UK.
Eur J Endocrinol. 2004 Jan;150(1):57-63. doi: 10.1530/eje.0.1500057.
A phase I single centre, open label study of the pharmacokinetics and tolerability of a buccal testosterone tablet (COL 1621) was carried out.
Twelve testosterone-deficient males were treated with the buccal tablet twice daily for 7 consecutive days. Multiple blood samples were drawn for testosterone, dihydrotestosterone (DHT), bioavailable testosterone and sex hormone-binding globulin (SHBG).
After COL 1621, means+/-S.D. serum testosterone level increased to a peak concentration of 26.6+/-5.8 nmol/l (7.7+/-1.7 ng/ml) at 4.8+/-5.8 h and stayed in the eugonadal range. Steady state was achieved within the first 24 h and was maintained in the normal range. The bioavailable testosterone, DHT and free testosterone index followed a pattern very similar to that of testosterone. The mean serum testosterone to DHT ratio was within the normal male range throughout treatment. There was only one treatment-related adverse event (headache). Two-thirds of patients indicated that treatment with COL 1621 was acceptable and that the tablet was convenient to use. Six patients (50.0%) preferred COL 1621 to their previous testosterone replacement therapy, two patients gave preference to their previous treatment and three patients found both treatments to be equally acceptable. Data for one patient was not available.
We conclude that COL 1621 can efficiently elevate serum testosterone and DHT levels in hypogonadal men within the first day of application, achieve a steady state within 24 h and maintain serum testosterone in the normal range with a twice-daily treatment regimen. COL 1621 provides an effective alternative oral testosterone replacement therapy that gives physiological levels of testosterone and is well tolerated by the patients.
开展一项关于口腔用睾酮片（COL 1621）药代动力学和耐受性的I期单中心开放标签研究。
12名睾酮缺乏男性连续7天每天两次接受口腔片治疗。采集多份血样检测睾酮、双氢睾酮（DHT）、生物可利用睾酮和性激素结合球蛋白（SHBG）。
服用COL 1621后，血清睾酮水平均值±标准差在4.8±5.8小时升至峰值浓度26.6±5.8 nmol/l（7.7±1.7 ng/ml），并维持在正常性腺功能范围内。在最初24小时内达到稳态，并保持在正常范围内。生物可利用睾酮、DHT和游离睾酮指数的变化模式与睾酮非常相似。整个治疗过程中血清睾酮与DHT的平均比值在正常男性范围内。仅出现1例与治疗相关的不良事件（头痛）。三分之二的患者表示接受COL 1621治疗，且该片剂使用方便。6名患者（50.0%）更倾向于COL 1621而非之前的睾酮替代疗法，2名患者更倾向于之前的治疗，3名患者认为两种治疗同样可以接受。1名患者的数据缺失。
我们得出结论，COL 1621可在应用第一天有效提高性腺功能减退男性的血清睾酮和DHT水平，24小时内达到稳态，每日两次治疗方案可使血清睾酮维持在正常范围内。COL 1621提供了一种有效的口服睾酮替代疗法，能使睾酮达到生理水平且患者耐受性良好。
