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|Titolo:||Plasma concentrations and pharmacokinetic parameters of nitrofenac using a simple and sensitive HPLC method|
|Autori interni:||BENONI, Giuseppina|
|Data di pubblicazione:||1995|
|Rivista:||JOURNAL OF PHARMACEUTICAL SCIENCES|
|Abstract:||An accurate and sensitive HPLC method has been developed for the determination of nitrofenac, a new, original diclofenac derivate showing a good tolerability and a wide anti-inflammatory profile, diclofenac, and its metabolites in plasma. This method has been applied to evaluate the pharmacokinetic parameters of the drugs, using a noncompartmental model, after the oral administration of 5 mg/kg nitrofenac to rats. Nitrofenac and the internal standard flufenamic acid were dissolved in acetonitrile, and diclofenac was dissolved in methanol. The drugs were eluted from a 5 microns LC-8 column with a mobile phase consisting of acetonitrile/water (50/50 v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL/min with UV detection at 280 nm for diclofenac and 275 nm for nitrofenac. The detection limit for the drugs in plasma was 25 ng/mL. The peak concentration of nitrofenac was reached 7 h after drug administration, while with diclofenac we observed three peaks at 2, 5, and 10 h; the mean residence time and the elimination rate constant for nitrofenac were 6.18 +/- 0.09 h and 0.37 +/- 0.03 h-1 respectively, while those for diclofenac were 12.24 +/- 0.11 h and 0.11 +/- 0.04 h-1. Under our conditions, the metabolism of nitrofenac produced 23% diclofenac and other metabolites: the plasma concentrations and kinetic characteristics of diclofenac are enough to induce an anti-inflammatory activity, while the clinical importance of the other metabolites remains to be elucidated.|
|Appare nelle tipologie:||01.01 Articolo in Rivista|
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