التفاصيل البيبلوغرافية
| العنوان: |
Pharmacokinetic Profile of 1-Methylnicotinamide Nitrate in Rats. |
| المؤلفون: |
Szafarz, Malgorzata1, Kus, Kamil2, Walczak, Maria2,3, Zakrzewska, Agnieszka2, Niemczak, Michal4, Pernak, Juliusz4, Chlopicki, Stefan2,5 stefan.chlopicki@jcet.eu |
| المصدر: |
Journal of Pharmaceutical Sciences. May2017, Vol. 106 Issue 5, p1412-1418. 7p. |
| مصطلحات موضوعية: |
*METABOLITE analysis, *NICOTINAMIDE, *PHARMACOKINETICS, *BIOAVAILABILITY, *LABORATORY rats |
| مستخلص: |
Treatment with 1-methylnicotinamide (MNA), a major metabolite of nicotinamide, exerts antithrombotic, anti-inflammatory, and vasoprotective effects. Yet, pharmacokinetic (PK) profile of MNA has not been fully characterized. In the present work, we analyze the PK profile of the MNA given as a nitrate (MNANO 3 ) in comparison to nitrite (MNANO 2 ) or chloride (MNACl) in rats. The bioavailability of MNA administered as MNANO 3 equaled 22.4% as compared to MNANO 2 or MNACl (9.2% and 9.1%, respectively). Moreover, in single-pass intestinal perfusion experiments, effective permeability of MNA given as MNANO 3 was higher as compared to MNA administered as MNANO 2 or MNACl. In turn, t max was the shortest and C max the highest (0.22 h and 56.65μM) for intragastrically administered MNANO 2 comparing to MNANO 3 (1.92 h, 21.74μM) or MNACl (0.63 h, 16.13μM). Transfer constant between central and peripheral compartments (k cp ) and volume of distribution (V ss ) for MNANO 3 (0.33 h −1 and 1.96 L/kg) were higher as compared to MNANO 2 or MNACl (0.11 h −1 , 0.08 h −1 for k cp and 1.05 L/kg, 0.76 L/kg for V ss , respectively). In conclusion, we characterized PK profile of MNA and demonstrated that nitrate ion augmented bioavailability and favorably modified PK profile of MNA. Furthermore, given vasoprotective properties of MNA as well as nitrate, MNANO 3 represents a bifunctional compound. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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