Mourad Sara S, El-Kimary Eman I, Barary Magda A, Hamdy Dalia A
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, El-Messalah, Alexandria 21521, Egypt.
AbEx Health Services Ltd, Edmonton, Alberta, Canada.
Bioanalysis. 2019 Jul;11(14):1321-1336. doi: 10.4155/bio-2018-0097. Epub 2019 Aug 1.
Assessment of pharmacokinetic interaction between linagliptin (LNG) and tadalafil (TDL) in healthy males. First, a novel LC-MS method was developed; second, a Phase IV, open-label, cross-over study was performed. Volunteers took single 20-mg TDL dose on day 1 followed by wash out period of 2 weeks then multiple oral dosing of 5-mg/day LNG for 13 days. On day 13, volunteers were co-administered 20-mg TDL. LNG and TDL single doses did not affect QTc interval. Smoking did not alter pharmacokinetics/pharmacodynamics of LNG and TDL. Co-administration of LNG with TDL resulted in TDL longer time to reach maximum plasma concentration (T), decreased oral clearance (Cl/F) and oral volume of distribution (Vd/F), increased its maximum plasma concentration (C), area under concentration-time curve (AUC), muscle pain and QTc prolongation. LNG and TDL co-administration warrants monitoring and/or TDL dose adjustment.
健康男性中利格列汀（LNG）与他达拉非（TDL）的药代动力学相互作用评估。首先，开发了一种新型液相色谱-质谱联用方法；其次，进行了一项IV期、开放标签、交叉研究。志愿者在第1天服用单次20毫克TDL剂量，随后有2周的洗脱期，然后连续13天每天口服5毫克LNG。在第13天，志愿者同时服用20毫克TDL。LNG和TDL单剂量均未影响QTc间期。吸烟未改变LNG和TDL的药代动力学/药效学。LNG与TDL联合给药导致TDL达到最大血浆浓度（T）的时间延长、口服清除率（Cl/F）和口服分布容积（Vd/F）降低、最大血浆浓度（C）、浓度-时间曲线下面积（AUC）增加、肌肉疼痛和QTc延长。LNG与TDL联合给药需要进行监测和/或调整TDL剂量。
