Study on safety and bioavailability of ubiquinol (Kaneka QH™) after single and 4-week multiple oral administration to healthy volunteers

Regulatory Toxicology and Pharmacology

Volumn 47, Issue 1, 2007, Pages 19-28

  Hosoe, Kazunori ^a   Kitano, Mitsuaki ^a   Kishida, Hideyuki ^a   Kubo, Hiroshi ^a   Fujii, Kenji ^a   Kitahara, Mikio ^a  

^a KANEKA CORPORATION   (Japan)

Author keywords

Bioavailability; Coenzyme Q10; Healthy volunteer; Safety; Ubiquinol; Ubiquinone

Indexed keywords

KANEKA QH; PLACEBO; UBIQUINOL; UBIQUINONE DERIVATIVE;

ABDOMINAL PAIN; ADULT; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; CENTRAL NERVOUS SYSTEM DISEASE; COMMON COLD; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG SAFETY; DRUG WITHDRAWAL; DYSMENORRHEA; ELECTROCARDIOGRAM; ENTEROCOLITIS; FEMALE; FROZEN SHOULDER; GASTROINTESTINAL DISEASE; GASTROINTESTINAL SYMPTOM; GINGIVA PAIN; GYNECOLOGIC DISEASE; HEADACHE; HEAT STROKE; HUMAN; HUMAN EXPERIMENT; JOINT STIFFNESS; LABORATORY TEST; LEUKOCYTOSIS; LOOSE FECES; LOW BACK PAIN; MALE; MENSTRUAL IRREGULARITY; MENTAL DISEASE; MUSCULOSKELETAL DISEASE; NAUSEA; NORMAL HUMAN; PERIPHERAL NEUROPATHY; PHYSICAL EXAMINATION; PRIORITY JOURNAL; RASH; RESPIRATORY TRACT DISEASE; SINGLE DRUG DOSE; SKIN APPENDAGE DISEASE; SOMNOLENCE; SORE THROAT; STOMACH PAIN; STOMATITIS; VITAL SIGN; WHIPLASH INJURY;

ACUTE TOXICITY TESTS; ADMINISTRATION, ORAL; ADULT; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; DIETARY SUPPLEMENTS; FEMALE; HUMANS; INTESTINAL ABSORPTION; MALE; SINGLE-BLIND METHOD; UBIQUINONE;

EID: 33751106205     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2006.07.001     Document Type: Article

References (62)

1. Arroyo A., Kagan V.E., Tyurin V.A., Burgess J.R., de Cabo R., Navas P., and Villalba J.M. NADH and NADPH dependent reduction of coenzyme Q at the plasma membrane. Antioxid. Redox. Signal. 2 (2000) 251-262
2. Åberg F., Appelkvist E.-L., Dallner G., and Ernster L. Distribution and redox state of ubiquinones in rat and human tissues. Arch. Biochem. Biophys. 295 (1992) 230-234
3. Baggio E., Gandini R., Plancher A.C., Passeri M., and Carmosino G. Italian mulitcenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. Molec. Aspects Med. 15 Supplement (1994) S287-S294
4. Battino M., Ferri E., Gorini A., Villa R.F., Huertas J.F.R., Fiorella P., Genova M.L., Lenaz G., and Marchetti M. Natural distribution and occurrence of coenzyme Q homologues. Memb. Biochem. 9 (1992) 179-190
5. Bogentoft C., Edlund P.O., Olsson B., Wilund L., and Westensen K. Biopharmaceutical aspects of intravenous and oral administration of coenzyme Q10. In: Folkers K., Littarru G.P., and Yamagami T. (Eds). Biomedical and Clinical Aspects of Coenzyme Q (1991), Elsevier Science, Amsterdam 215-224 (Chapter 6)
6. Cabrini L., Barzanti V., Cipollone M., Fioretini D., Grossi G., Tolomelli B., Zambonin L., and Landi L. Antioxidants and total peroxyl radical-trapping ability of olive and seed oils. J. Agric. Food Chem. 49 (2001) 6026-6032
7. Chiba T., Watanabe T., Kume Y., Sugiyama K., and Shiojiri H. Toxicological studies of ubiquinone-10 (I). Acute toxicity test in rats and mice and subacute and chronic toxicity tests in rats. Oyo Yakuri 6 (1972) 769-779 (Abstract in English)
8. Chiba T., Sugiyama K., Kume Y., Shiojiri H., Watanabe T., and Ozeki M. Toxicological studies of ubiquinone-10 (II) subacute toxicity test in rabbits. Oyo Yakuri 6 (1972) 781-786 (Abstract in English)
9. Chopra R.K., Goldman R., Sinatra S.T., and Bhagavan N.H. Relative bioavailavility of coenzyme Q10 formulations in human subjects. Int. J. Vitam. Nutr. Res. 68 (1998) 109-113
10. Crane F.L. Biochemical functions of coenzyme Q10. J. Am. Coll. Nutr. 20 (2001) 591-598
11. Ferrante K.L., Shefner J., Zhang H., Betensky R., O'Brien M., Yu H., Fantasia M., Taft J., Beal M.F., 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 (2005) 1834-1836
12. Feigin A., Kieburtz K., Como P., Hickey C., Claude K., Abwender D., Zimmerman C., Steinberg K., and Shoulson I. Assessment of coenzyme Q10 tolerability in Huntington's disease. Mov. Disord. 11 (1996) 321-323
13. Forsmark-Andree P., Lee C.-P., Dallner G., and Ernster L. Lipid peroxidation and changes in the ubiquinone content and the respiratory chain enzymes of submitochondrial particles. Free Radic. Biol. Med. 22 (1997) 391-400
14. Frei B., Kim M.C., and Ames B.N. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc. Natl. Acad. Sci. 87 (1990) 4879-4883
15. Fujii, K., Kubo, H., Kawabe, T., Matsumoto, S., Hosoe, K., In press. Determination of ubiquinol (reduced form of Coenzyme Q10) content in foods. J. Agric. Food Chem.
16. Greenberg S., and Frishman W.H. Coenzyme Q10: A new drug for cardiovascular disease. J. Clin. Pharmacol. 30 (1990) 596-608
17. In: Hendler S.S., and Rorvik M.S. (Eds). PDR for Nutritional Supplements (2001), Medical Economics, Montvale, New Jersey 103-106
18. Hodges S., Hertz N., Lockwood K., and Lister R. CoQ10: Could it have a role in cancer management?. BioFactors 9 (1999) 365-370
19. Hofman-Bang C., Rehnquist N., Swedberg K., Wiklund I., and Åström H. Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. J. Cardiac Failure 1 (1995) 101-107
20. Huntington Study Group. 2001. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurol. 57, 397-404.
21. Ikematsu H., Nakamura K., Harashima S.I., Fujii K., and Fukutomi N. Safety assessment of coenzyme Q10 (Kaneka Q10) in healthy subjects: A double-blind, randomized, placebo-controlled trial. Regul. Toxicol. Pharmacol. 44 (2006) 212-218
22. Jones K., Hughes K., Mischley L., and McKenna D.J. Coenzyme Q10: Efficacy, safety, and use. Alternat. Ther. 8 (2002) 42-55
23. Joshi S.S., Sawant S.V., Shedge A., and Halpner A.D. Comparative bioavailability of two novel coenzyme Q10 preparations in humans. Int. J. Clin. Pharm. Therp. 41 (2003) 42-48
24. Kagan V.E., Fabisiak J.P., and Tyurina Y.Y. In: Kagan V.E., and Quinn P.J. (Eds). Coenzyme Q: Molecular Mechanisms in Health and Disease (2001), CRC Press, New York 119-129
25. a. Subchronic Oral Toxicity of Ubiquinol in Rats. Food. Chem. Toxicol.
26. b. Subchronic Oral Toxicity of Ubiquinol in Dogs. Food. Chem. Toxicol.
27. c. Evaluation of the Mutagenic and Genotoxic Potential of Ubiquinol. Genet. Toxicol. Environ. Mutagen.
28. Kurowska E.M., Dresser G., Deutsch L., Bassoo E., and Freeman D.J. Relative bioavailavility and antioxidant potential of two coenzyme Q10 preparations. Ann. Nutr. Metab. 47 (2003) 16-21
29. Lansjoen P.H., Langsjoen P.H., and Folkers K. Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. Am. J. Cardiol. 65 (1990) 521-523
30. Lass A., and Sohal R.S. Effect of coenzyme Q10 and a-tocopherol content of mitochndria on the production of superoxide anion radicals. FASEB J. 14 (2000) 87-94
31. Lücker P.W., Wetzelsberger N., Hennings G., and Rehn D. Pharmacokineics of coenzyme ubidecarenone in healthy volunteers. Biomed. Clin. Aspects CoQ vol. 4 (1984) 143-151 Elsevier Science
32. Mae, T., Sakamoto, Y., Morikawa, S., Hidaka, T., 2001. Pharmaceutical composition comprising coenzyme Q10. US Patent, No. 6,184,255 B1.
33. Miles M.V., Horn P., Miles L., Tang P., Steele P., and DeGrauw T. Bioequivalence of coenzyme Q10 from over-the-counter supplements. Nutr. Res. 22 (2002) 919-929
34. Mohr D., Bowry V.W., and Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low density lipoprotein to the initiation of lipid peroxidation. Biochim. Biophys. Acta 1126 (1992) 247-254
35. Mugford C.A., and Kedderis G.L. Sex-dependent metabolism of xenobiotics. Drug Metab. Rev. 30 (1998) 441-498
36. Noack H., Kube U., and Augustin W. Relations between tocopherol depletion and coenzyme Q during lipid peroxidation in rat liver mitochondria. Free Radic. Res. 20 (1994) 375-386
37. Nohl H., Kozlov A.V., Staniek K., and Gille L. The multiple functions of coenzyme Q. Bioorg. Chem. 29 (2001) 1-13
38. Notake Y., Tamura S., Toyoshima S., Fujita H., Suzuki Y., and Chiba T. Effects of coenzyme Q10 on development of the fetuses and neonates in rats and mice. Iyakuhin Kenkyu 3 (1972) 306-315 (Abstract in English)
39. Oda, S., 2003. Single-dose oral toxicity study of ubiquinol in rats. Study No. B-4984, Bozo Research Center Inc., Tokyo, Japan. Final Report, March 27, 2003 (Unpublished).
40. Overvad K., Diamant B., Holm L., Hølmer G., Mortensen S.A., and Stender S. Coenzyme Q10 in health and disease. Eur. J. Clin. Nutr. 53 (1999) 764-770
41. Okamoto T., Matsuya T., Fukunaga Y., Kishi T., and Yamagami T. Human serum ubiquinol-10 and relationship to serum lipids. Internat. J. Vit. Nutr. Res. 59 (1989) 288-292
42. Pepping J. Coenzyme Q10. Am. J. Health Syst. Pharm. 56 (1999) 519-521
43. Quinn P.J., Fabisiak J.P., and Kagan V.E. Expansion of antioxidant function of vitamine E by coenzyme Q. BioFactors 9 (1999) 149-154
44. Ramasarma T. Natural occurrence and distribution of coenzyme Q. In: Lenaz G. (Ed). Coenzyme Q: Biochemical, Bioenergetics and Clinical Applications of Usbiquinone (1985), John Wiley & Sons, New York 67-81
45. Shapiro B.H., Agrawal A.K., and Pampori N.A. Gender differences in drug metabolism regulated by growth hormone. Int. J. Biochem. Cell Biol. 27 (1995) 9-20
46. Singh R.B., Niaz M.A., Rastogi V., and Rastogi S.S. Coenzyme Q10 in cardiovascular disease. JAPI 46 (1998) 299-306
47. Shults C.W., Beal M.F., Fontaine D., Nakano K., and Haas R.H. Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients. Neurol. 50 (1998) 793-795
48. Shults C.W., Beal M.F., Song D., and Fontaine D. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease. Exper. Neurol. 188 (2004) 491-494
49. Shults C.W., Oakes D., Kieburtz K., Beal M.F., Hass R., Plumb S., Juncos J.L., Nutt J., Shoulson I., Carter J., Kompoliti K., Perlmutter J.S., Reich S., Stern M., Watts R.L., Kurlan R., Molho E., Harrison M., Lew M., and the Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: Evidence of slowing of the functional decline. Arch. Neurol. 59 (2002) 1541-1550
50. Stocker R., and Suarna C. Extracellular reduction of ubiquinone-1 and -10 by human Hep G2 and blood cells. Biochim. Biophys. Acta 1158 (1993) 15-22
51. Tomasetti M., Alleva R., Solenghi M.D., and Littaru G.P. Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ration as a possible marker of increased risk of atherosclerosis. BioFactors 9 (1999) 231-240
52. Tomono Y., Hasegawa J., Seki T., and Morishita N. Pharmacokinetic study of deuterium-labeled coenzyme Q10 in man. Int. J. Clin. Pharmacol. Ther. Toxicol. 24 (1986) 536-541
53. Tran M.T., Mitchell T.M., Kennedy D.T., and Giles J.T. Role of coenzyme Q10 in chronic heart failure, angina, and hypertension. Pharmacotherapy 21 (2001) 797-806
54. Turunen M., Appelkvist E.-L., Sindelar P., and Dallner G. Blood concentration of coenzyme Q10 increases in rats when esterified forms are administered. J. Nutr. 129 (1999) 2113-2118
55. ®. J. Med. Food 8 (2005) 397-399
56. Villalba J.M., pez-Lluch G.L., Santos-OcaZa C., RodrRguez-Aguilera J.C., and Navas P. Extramitochondrial functions of coenzyme Q. In: Kagan V.E., and Quinn P.J. (Eds). Coenzyme Q: Molecular Mechanisms in Health and Disease (2001), CRC Press, New York 83-94
57. Weber C., Jakobsen T.S., Mortensen S.A., Paulsen G., and Hølmer G. Effect of dietary coenzyme Q10 as an antioxidant in human plasma. Molec. Aspects Med. 15 (1994) s97-s102
58. Weis M., Mortensen S.A., Rassing M.R., Moller-Sonnergaard J., Poulsen G., and Rasmussen S.N. Bioavailability of four oral Coenzyme Q10 formulations in healthy volunteers. Mol. Aspects Med. 15 (1994) 273-280
59. Williams, K.D., 1995. Acute oral gavage lethality study with ubiquinone in rats. Unpublished study. Study Identification: HWI 6510-136. Covance Laboratories, Inc., Madison, Wisconsin (Unpublished).
60. Williams K.D., Maneke J.D., AbdelHameed M., Hall R.L., Palmer T.E., Kitano M., and Hidaka T. 52-Week oral gavage chronic toxicity study with ubiquinone in rats with a 4-week recovery. J. Agric. Food Chem. 47 (1999) 3756-3763
61. Yamashita S., and Yamamoto Y. Simultaneous detection of ubiquinol and ubiquinone in human plasma as marker of oxidative stress. Anal. Biochem. 250 (1997) 66-73
62. 14C]Coenzyme Q10 from the liver to other tissue after intravenous administration to guinea pigs. Biochim. Biophys. Acta 759 (1983) 286-291