Jehle Sigrid, Reyes Carlos M, Sundeen Robert E, Freda Pamela U
Department of Medicine, Columbia College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA.
J Clin Endocrinol Metab. 2005 Mar;90(3):1588-93. doi: 10.1210/jc.2004-1967. Epub 2004 Dec 7.
IGF-I levels normalize in the majority of patients with acromegaly treated with the GH receptor antagonist pegvisomant. To date, the efficacy of pegvisomant has been demonstrated with daily administration of doses ranging from 10 to 40 mg. However, given the known long half-life of the drug in circulation, we hypothesized that dosing less frequently than daily would still maintain the drug's efficacy. We studied 10 patients with active acromegaly treated with pegvisomant. This therapy was begun at 10 mg daily but then titrated up in dose or down to alternate-day dosing to try to maintain serum IGF-I levels in the upper half of the patients' age-adjusted normal range. We found that in five of 10 patients, serum IGF-I levels remained normal on less frequent than daily pegvisomant. Signs and symptoms of the disease and a disease-related morbidity, insulin resistance, remained improved in these patients. We demonstrate for the first time the continued efficacy of alternate-day administration of pegvisomant.
使用生长激素(GH)受体拮抗剂培维索孟治疗的大多数肢端肥大症患者的胰岛素样生长因子-I(IGF-I)水平恢复正常。迄今为止,已证明每日给予10至40毫克剂量的培维索孟是有效的。然而,鉴于该药物在循环中的半衰期已知较长,我们推测给药频率低于每日一次仍能维持药物疗效。我们研究了10例接受培维索孟治疗的活动性肢端肥大症患者。该治疗开始时每日10毫克,但随后调整剂量或改为隔日给药,以试图将血清IGF-I水平维持在患者年龄调整后的正常范围的上半部分。我们发现,10例患者中有5例,培维索孟给药频率低于每日一次时,血清IGF-I水平仍保持正常。这些患者的疾病体征和症状以及与疾病相关的发病率——胰岛素抵抗——仍有所改善。我们首次证明了培维索孟隔日给药的持续疗效。