Abstract
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.
Similar content being viewed by others
References
AHFS (American Society of Health-System Pharmacists), AHFS drug information. Board of the AHFS, Bethesda (2007).
Blank, J., Tucker, A., Sweatlock, J., Gasiewicz, T., and Luster, M., Alpha-naphthoflavone antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced murine lymphocyte ethoxyresorufin-O-deethylase activity and immunosuppression. Mol. Pharmacol., 32, 169–172 (1987).
Bonakdar, R. and Guarneri, E., Coenzyme Q10. Am. Fam. Phys., 72, 1065–1070 (2005).
Bonuccelli, U. and Del Dotto, P., New pharmacologic horizons in the treatment of Parkinson disease. Neurology, 67(7 Suppl 2), S30–S38 (2006).
Brunton, R., Lazo, J., and Parker, K., Goodman and Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, New York (2005).
Buettner, C., Phillips, R., Davis, R., Gardiner, P., and Mittleman, M., Use of dietary supplements among United States adults with coronary artery disease and atherosclerotic risks. Am. J. Cardiol., 99, 661–666 (2007).
Conklin, K., Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integr. Cancer Ther., 4, 110–130 (2005).
Crane, F., Biochemical functions of coenzyme Q10. J. Am. Coll. Nutr., 20, 591–598 (2001).
Ferrante, K., Shefner, J., Zhang, H., Betensky, R., O’Brien, M., Yu, H., Fantasia, M., Taft, J., Beal, M., Traynor, B., Newhall, K., Donofrio, P., Caress, J., Ashburn, C., Freiberg, B., O’Neill, C., Paladenech, C., Walker, T., Pestronk, A., Abrams, B., Florence, J., Renna, R., Schierbecker, J., Malkus, B., and Cudkowicz, M., Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology, 65, 1834–1836 (2005).
Gardiner, P., Graham, R., Legedza, A., Eisenberg, D., and Phillips, S., Factors associated with dietary supplement use among prescription medication users. Arch. Intern. Med., 166, 1968–1974 (2006).
Gardiner, P., Phillips, R., and Shaughnessy, A., Herbal and dietary supplement-drug interactions in patients with chronic illnesses. Am. Fam. Physician, 77, 73–78 (2008).
Greenberg, S. and Frishman, W. Co-enzyme Q10: a new drug for cardiovascular disease. J. Clin. Pharmacol., 30, 596–608 (1990).
Hodgson, J., Watts, G., Playford, D., Burke, V., and Croft, K., Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur. J. Clin. Nutr., 56, 1137–1142 (2002).
Hyun, D., Emerson, S., Jo, D., Mattson, M., and de Cabo, R., Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging. Proc. Natl. Acad. Sci. USA, 103, 19908–19912 (2006).
Janson, M., Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging. Clin. Interv. Aging, 1, 261–265 (2006).
Kaminsky, L. and Zhang, Z., Human P450 metabolism of warfarin. Pharmacol. Ther., 73, 67–74 (1997).
Koch, K., Ricci, B., Hedayetullah, N., Jewell, D., and Kersey, K., Effect of alosetron on theophylline pharmacokinetics. Br. J. Clin. Pharmacol., 52, 596–600 (2001).
Laaksonen, R., Ojala, J., Tikkanen, M., and Himberg, J., Serum ubiquinone concentrations after short-and long-term treatment with HMG-CoA reductase inhibitors. Eur. J. Clin. Pharmacol., 46, 313–317 (1994).
Landbo, C. and Almdal, T., Interaction between warfarin and coenzyme Q10. Ugeskr. Laeger., 160, 3226–3227 (1998).
Leonhauser, S., Lebold, K., Krisch, K., Standinger, H., Gale, F., Page, A. Jr., and Folkers, K., Arch. Biochem. Biophys., 96, 580–586 (1962).
Levy, G., Kaufmann, P., Buchsbaum, R., Montes, J., Barsdorf, A., Arbing, R., Battista, V., Zhou, X., Mitsumoto, H., Levin, B., and Thompson, J., A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS. Neurology, 66, 660–663 (2006).
Littarru, G. and Tiano, L., Clinical aspects of coenzyme Q10: an update. Curr. Opin. Clin. Nutr. Metab. Care, 8, 641–646 (2005).
Ratnam, D., Ankola, D., Bhardwaj, V., Sahana, D., and Kumar, M., Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J. Control. Release, 113, 189–207 (2006).
Roffe, L., Schmidt, K., and Ernst, E., Efficacy of coenzyme Q10 for improved tolerability of cancer treatments: a systematic review. J. Clin. Oncol., 22, 4418–4424 (2004).
Sassi, S., Genova, M., and Lenaz, G., Exogenous CoQ10 preserves plasma ubiquinone levels in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Int. J. Clin. Lab. Res., 24, 171–176 (1994).
Shults, C. and Haas, R., Clinical trials of coenzyme Q10 in neurological disorders. Biofactors, 25, 117–126 (2005).
Shults, C., Flint Beal, M., Song, D., and Fontaine, D., Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson’s disease. Exp. Neurol., 188, 491–494 (2004).
Singh, U., Devaraj, S., and Jialal, I., Coenzyme Q10 supplementation and heart failure. Nutr. Rev., 65(6 Pt 1), 286–293 (2007).
Smith, K., Matson, S., Matson, W., Cormier, K., Del Signore, S., Hagerty, S., Stack, E., Ryu, H., and Ferrante, R., Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington’s disease mice. Biochim. Biophys. Acta, 1762, 616–626 (2006).
Sun, I., Sun, E., Crane, F., Morro, D., Lindgren, A., and Low, H., Requirement for coenzyme Q in plasma membrane electron transport. Proc. Natl. Acad. Sci. USA, 89, 11126–11130 (1992).
Tang, J., Sun, J., Zhang, Y., Li, L., Cui, F., and He, Z., Herb-drug interactions: Effect of Ginkgo biloba extract on the pharmacokinetics of theophylline in rats. Food Chem. Toxicol., 45, 2441–2445 (2007).
Tjia, J., Colbert, J., and Back, D., Theophylline metabolism in human liver microsomes: inhibition studies. J. Pharmacol. Exp. Ther., 276, 912–917 (1996).
Tran, M., Mitchell, T., Kennedy, D., and Giles, J., Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy, 21, 797–806 (2001).
Yang, H., Lin, S., Huang, S., and Chou, H., Acute administration of red yeast rice (Monascus purpureus) depletes tissue coenzyme Q(10) levels in ICR mice. Br. J. Nutr., 93, 131–135 (2005).
Yong, J., Florkowski, C., Molyneux, S., McEwan, R., Frampton, C., George, P., and Scott, R., Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia. Am. J. Cardiol., 100, 1400–1403 (2007).
Zhou, Q., Zhou, S., and Chan, E., Effect of coenzyme Q10 on warfarin hydroxylation in rat and human liver microsomes. Curr. Drug Metab., 6, 67–81 (2005).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Baskaran, R., Shanmugam, S., Nagayya-Sriraman, S. et al. The effect of coenzyme Q10 on the pharmacokinetic parameters of theophylline. Arch. Pharm. Res. 31, 938–944 (2008). https://doi.org/10.1007/s12272-001-1250-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-001-1250-1