Effect of coenzyme Q10 on the disposition of doxorubicin in rats

Abstract

The effect of exogenous coenzyme Q10 (CoQ10) on the pharmacokinetic profiles and biliary excretion of doxorubicin and its main metabolites, doxorubicinol and doxorubicinolone, was investigated in rats. No statistically significant changes in the pharmacokinetic parameters of doxorubicin was observed following the intravenous bolus administration of 10 mg/kg doxorubicin to rats during a 6-day oral regimen of CoQ10 (20 mg/kg daily). Treatment with CoQ10 did not affect the formation of the doxorubicinol, but produced a 75% increase (P < 0.05) in the AUC of doxorubicinolone. Correspondingly, CoQ10 had no apparent effect on the biliary excretion of doxorubicin and formation clearance of doxorubicinol, whereas the formation clearance of doxorubicinolone was significantly increased by 69% in CoQ10-pretreated rats (P < 0.05). Overall, the results suggest that CoQ10 treatment has no significant effect on the pharmacokinetics of doxorubicin and the formation of the cytotoxic metabolite, doxorubicinol.

Effect of Coenzyme-Q10 on Doxorubicin-Induced Nephrotoxicity in Rats

“…The enhanced renal antioxidant status resulting from low dose CoQ10 prophylactic treatment could explain its nephroprotective effect. Such nephroprotective effect is probably not accompanied by any alteration in Dox disposition, including metabolism, biliary excretion, and clearance [23], nor with deterioration in Dox antineoplastic properties as reported in breast cancer cell cultures [24]. …”

Development of a CD‐MEKC method for investigating the metabolism of tamoxifen by flavin‐containing monooxygenases and the inhibitory effects of methimazole, nicotine and DMXAA

“…6-OH-MXAA on the other hand results from 6-methyl hydroxylation by CYP1A2. FMO3 has also exhibited catalytic activity towards the formation of 6-OH-MXAA and MMI has inhibited 35% of the hydroxylation verifying this activity [39].…”

“…Interestingly, DMXAA inhibited the reaction of TAM catalysed by FMO1, although no activity of FMO1 containing microsomes was reported towards the DMXAA hydroxylation [39]. The inhibition increased up to 51.1 M DMXAA and then started to decrease and inhibition was almost the same at DMXAA concentrations of 119.…”

“…The inhibition increased up to 51.1 M DMXAA and then started to decrease and inhibition was almost the same at DMXAA concentrations of 119. 2 [39].…”

Protective effect of coenzyme Q10 against doxorubicin-induced cardiotoxicity: Scoping review article

“…Two of the 14 (14.2 %) articles focus on survival and oxygen uptake and their conclusion was not clear and needs further investigation ( Aldridge, 1960 , Tábora et al, 1986 ). One of the articles (7.1 %) focuses on the effect of coenzyme Q10 on the pharmacokinetics of doxorubicin, the results showed that coenzyme Q10 will not increase the excretion of doxorubicin and it will not affect its cytotoxicity on cancer cells ( Zhou and Chowbay, 2002 ). Two of the articles (14.2 %) had insufficient data to conclude that coenzyme Q10 can protect against doxorubicin cardiac toxicity, The Second study that had insufficient data focused on change in QRS and concluded that coenzyme Q10 may decrease some of the toxicity of doxorubicin ( Folkers et al, 1978 ).…”