A pharmacokinetic drug-drug interaction study between pregabalin and tramadol in healthy volunteers
Combination therapy of pregabalin and tramadol is used to treat chronic neuropathic pain; however, the pharmacokinetic (PK) interactions of these drugs has not been studied. This study aimed to evaluate PK interactions between pregabalin and tramadol and the safety of combination therapy.
A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence cross-over study was conducted in healthy subjects. All subjects received the following three treatments for 4 days in each period: pregabalin 150 mg twice daily; tramadol extended-release (ER) 200 mg in the morning, and 100 mg in the evening; and co-administration of pregabalin 150 mg and tramadol ER 200 mg in the morning, and pregabalin 150 mg and tramadol ER 100 mg in the evening.
A total of 21 subjects completed the study with no clinically significant safety issues. For pregabalin, the geometric mean ratio (GMR) (90% CI; confidence interval) of combination therapy to monotherapy for maximum concentration at steady state (Cmax,ss) and area under the concentration curve from 0 to dosing interval time at steady state (AUCτ,ss) were 0.8801 (0.8043–0.9632) and 1.0830 (1.0569–1.1098), respectively. The corresponding values for tramadol were 1.0177 (0.9839–1.0526) and 1.0152 (0.9896–1.0414), respectively. The GMR (90% CI) of combination therapy to monotherapy of O-desmethyl-tramadol for Cmax,ss and AUCτ,ss was 1.0465 (1.0095–1.0848) and 1.0361 (1.0001–1.0734), respectively.
There were no significant drug interactions between pregabalin and tramadol, considering that all of the 90% CI of PK measures were within the conventional bioequivalence range. Both drugs were well tolerated when administered concomitantly.
KeywordsDrug-drug interactions Pharmacokinetics Pregabalin Tramadol
Guarantor of the article: Seonghae Yoon.
Building the study concept: Yun Kim, Guangjin Im, Jae-Yong Chung, Seonghae Yoon.
Study design and acquisition of data: Yun Kim, Guangjin Im, Jae-Yong Chung, and Seonghae Yoon.
Data analysis and interpretation: Soyoung Lee, Yun Kim, Janice Ji Sung Lee, Guangjin Im, Joo-Youn Cho, Jae-Yong Chung, and Seonghae Yoon.
Drafting this manuscript: Soyoung Lee.
Final editing of the manuscript: Soyoung Lee, Yun Kim, Janice Ji Sung Lee, Guangjin Im, Joo-Youn Cho, Jae-Yong Chung, and Seonghae Yoon.
This study was sponsored by SamChunDang Pharm. Co., Ltd., Seoul, Republic of Korea.
Compliance with ethical standards
This study was approved by the institutional review board of Seoul National University Bundang Hospital, Republic of Korea (no. B-1604-341-006) and registered with the Clinical Research Information Service (KCT 0002657). All subjects provided their written informed consent form prior to participating in this study. The study was conducted in compliance with the Declaration of Helsinki and followed the Guideline of Good Clinical Practice.
Conflict of interest
Janice Ji Sung Lee and Guangjin Im are employees of SamChunDang Pharm. Co., Ltd., Seoul, Republic of Korea, but the other authors have no competing interests to declare.
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