Zierler-Brown Seena L, Kyle Jeffrey A
Department of Pharmacy Practice, Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL, USA.
Ann Pharmacother. 2007 Jan;41(1):95-9. doi: 10.1345/aph.1H310. Epub 2006 Dec 26.
To review the pharmacology, pharmacokinetics, efficacy, and safety of varenicline and provide a review of relevant clinical data.
A MEDLINE search (2001-December 2006) was conducted using the key words varenicline and nicotine replacement therapy for clinical trials limited to human subjects and published in English.
All available human trials of varenicline were selected for review. References cited in identified articles were used for additional citations.
Varenicline selectively targets the alpha4beta2 nicotine receptors in the brain that are responsible for cravings and withdrawal associated with nicotine use and dependence. Maximal plasma concentration occurs within 3-4 hours after administration and, after multiple doses, a steady-state concentration is reached within 4 days. Varenicline has a half-life of 24 hours. Oral bioavailability is not affected by food or time of administration. It exhibits linear pharmacokinetics and low plasma protein binding (< or =20%) regardless of a patient's age and renal status. It can be administered once daily. Dosage adjustments are not required in patients with hepatic insufficiency, but adjustments may be necessary in patients with severe renal insufficiency. Clinically significant drug-drug interactions have not been observed with varenicline or co-inhibitors of the human organic cation transporter, which mediates renal secretion of varenicline. Substrates such as warfarin, digoxin, cimetidine, metformin, bupropion, and transdermal nicotine do not alter pharmacokinetic parameters when coadministered with varenicline. In vitro studies have not demonstrated alterations in cytochrome P450 enzyme parameters. Varenicline's safety with coadministration of nicotine replacement products has not been well established.
Varenicline is an effective oral agent for smoking cessation.
综述伐尼克兰的药理学、药代动力学、疗效及安全性，并对相关临床数据进行回顾。
利用关键词“伐尼克兰”和“尼古丁替代疗法”对MEDLINE（2001年至2006年12月）进行检索，纳入仅限于人类受试者且以英文发表的临床试验。
选取所有已有的伐尼克兰人体试验进行综述。对已识别文章中引用的参考文献用于进一步的文献引用。
伐尼克兰选择性作用于大脑中的α4β2尼古丁受体，这些受体与尼古丁使用及依赖相关的渴望和戒断反应有关。给药后3 - 4小时达到最大血浆浓度，多次给药后，4天内达到稳态浓度。伐尼克兰的半衰期为24小时。口服生物利用度不受食物或给药时间的影响。无论患者年龄和肾功能状态如何，其呈现线性药代动力学且血浆蛋白结合率低（≤20%）。它可以每日给药一次。肝功能不全患者无需调整剂量，但严重肾功能不全患者可能需要调整剂量。未观察到伐尼克兰与介导伐尼克兰肾脏分泌的人类有机阳离子转运体的共同抑制剂之间存在具有临床意义的药物相互作用。与伐尼克兰合用时，华法林、地高辛、西咪替丁、二甲双胍、安非他酮和经皮尼古丁等底物不会改变药代动力学参数。体外研究未显示细胞色素P450酶参数有改变。伐尼克兰与尼古丁替代产品合用的安全性尚未明确确立。
伐尼克兰是一种有效的戒烟口服药物。
