Arch Pharm Res Vol 31, No 7, 938-944, 2008 DOI 10.1007/s12272-001-1250-1 938 http://apr.psk.or.kr The Effect of Coenzyme Q10 on the Pharmacokinetic Parameters of Theophylline Rengarajan Baskaran, Srinivasan Shanmugam, Santhoshkumar Nagayya-Sriraman, Ju Hyun Kim, Tae Chun Jeong, Chul Soon Yong, Han-Gon Choi, and Bong Kyu Yoo College of Pharmacy, Yeungnam University, Kyungbuk 712-749, Korea (Received April 1, 2008/Revised May 27, 2008/Accepted June 12, 2008) Interaction of a drug with other drugs and dietary supplements is becoming an emerging issue for patients and health insurance authorities due to awareness of adverse drug event. In this study, we examined the effects of coenzyme Q10 (CoQ10), one of the most popular dietary supplements, on the pharmacokinetic parameters of theophylline in rats. The pharmacokinetic parameters of theophylline changed significantly when the drug was administered after five consecutive days of pretreatment with CoQ10. Time to reach maximum plasma concentration of theophylline delayed when the drug was administered after the pretreatment with CoQ10. Maximum plasma concentration and area under the curve of theophylline were about two-fold increased and other pharmacokinetic parameters such as half-life and volume of distribution were also changed significantly. Therefore, although CoQ10 is generally considered a safe dietary supplement, it appears that patients on theophylline therapy should use caution when they take CoQ10. Key words: Theophylline, Coenzyme Q10, Pharmacokinetic parameters, Protein binding, Cytochrome P450, INTRODUCTION Coenzyme Q10 (CoQ10) is a fat-soluble quinone com- pound commonly known as ubiquinone. The chemical structure of CoQ10 is 2,3-dimethoxy-5-methyl-6-decaprenyl- 1,4-benzoquinone in all-trans configuration (Fig. 1, Greenberg and Frishman, 1990; Tran et al., 2001). CoQ10 is found anywhere in the body, and is found in high concentrations in tissues with high energy turnover such as heart, brain, liver, and kidney (Bonakdar and Guarneri 2005; Leonhauser et al., 1962; Sun et al., 1992). CoQ10 has a fundamental role in cellular bioenergetics as a cofactor of the oxidative phosphorylation process in the mitochondria for the production of ATP. Furthermore, CoQ10 in its reduced form (ubiquinol) is a potent lipophilic antioxidant and is capable of recycling and regenerating other antioxidants such as tocopherol and ascorbate (Hyun et al., 2006). Other important function of CoQ10 includes expression of genes involved in the cell signaling (Crane 2001). CoQ10 is available as over-the-counter dietary supple- ment and is one of the most commonly used supplements in most developed countries. Potential benefits of CoQ10 supplementation have been recognized in the manage- ment of patients with cardiovascular and neurodegen- erative diseases such as heart failure and Parkinson’s diseases (Singh et al., 2007; Littarru and Tiano, 2005; Bonuccelli and Del Dotto, 2006; Janson, 2006; Buettner et al., 2007; Shults et al., 2004; Shults and Haas, 2005). A number of randomized controlled trials were performed and found improvement in several clinical parameters related to heart failure, including frequency of hospitaliza- Correspondence to: Bong Kyu Yoo, College of Pharmacy, Yeung- nam University, 214-1 Dae-dong, Kyungsan, Kyungbuk, 712-749, Korea Tel: 82-53-810-2822, Fax: 82-53-810-4654 E-mail: byoo@ynu.ac.kr Fig. 1. Chemical structure of coenzyme Q10