Pharmacokinetic interaction of Thymoquinone with ethanolic and acetonic extract of seeds of Nigella sativa Linn

[Speaker] Jayachandran Nair CV:1
[Co-author] Ujjalkumar Das:2, Rajani Mathur:1, Thirumurthy Velpandian:2
1:Department of Pharmacology, Delhi Institute of Pharmaceutical Science and Research, New Delhi, India, 2:Ocular Pharmacology and Pharmacy Division, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Thymoquinone (TQ) is principal constituent of seeds of Nigella sativa Linn(NS)· Owing to the high plasma protein binding (>99·99%) property of TQ, it poses a challenge in its analytical detection in biological matrix· Due to which true pharmacokinetic(PK) parameter of TQ could not be established· Therefore, we studied the PK behavior of TQ and its interaction with NS extracts after oral administration in rats·
For PK studies of the free drug in rat plasma, three vehicles namely, Acetonic NS (ANS), Ethanolic NS (ENS) and 0·5%w/v carboxymethylcellulose (CMC) media were selected· The doses for TQ in all vehicles were adjusted to 20mgKg-1 body weight after quantifying the levels of TQ in extracts· Thus, ANS-F, ENS-F and CMC-F were prepared, respectively. Wistar rats (n=5) were orally fed with each formulation and the PK parameters were studied in the plasma ultra-filtrate up to 12h·
The LOD and LLOQ of TQ, as estimated using LC-ESI-MRM/MS, were found to be 0·32 and 0·98 ngmL-1, respectively.· In ANS and ENS, the concentration of TQ was 6720±200 and 3833·33±50·33 µgmL-1, respectively· PK study showed rapid absorption of TQ within 0·5h in all groups· When compared to CMC-F group, at 1h post-dosage, free TQ in ENS-F group showed significant increase up to 4·05-fold (p=0·002) whereas, in ANS-F group, there was non-significant rise of TQ level, upto 1·74-fold· CMC-F group showed 2nd absorption phase at 2h followed by elimination over the period of 12h whereas in other formulations, there was a decline in TQ concentration at adjacent time points, which was significant at 3h (p<0·05)· In case of ANS-F and ENS-F both showed a significant rise in the TQ at 4h (p=0·0035) whereas TQ in ENS-F showed a third significant rise at 8h (p<0·0001) when compared to CMC-F group· Half-life & Tmax was maximum in CMC-F whereas AUC(0-12h) was highest for ENS-F· This may be due to low clearance of ENS-F(0·14±0·01Lh-1kg-1
For the first time, the plasma PK of free TQ from NS was studied using LC-ESI-MRM/MS· ENS-F showed comparatively, better bioavailability, suggesting that the alcoholic vehicle can improvise the currently available formulation development·

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