The aim of the present study was to evaluate the effect of multiple-dose paroxetine upon the pharmacokinetic profile of carvedilol in rats. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of paroxetine or after a pre-treatment with multiple oral doses of paroxetine (7.14 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. After carvediol co-administration with paroxetine, an approximately 4.5-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of AUC0-∞. Furthermore, an increase by 72% of peak plasma concentration was found, as well as an augmentation by 91% of the half life time of carvedilol was observed. Paroxetine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition.
Stability studies of the formulations of CAR solid dispersions were analyzed at 300C/65%RH for a period of three months. A simple reverse phase HPLC was developed and validated for the quantification of CAR solid dispersions. Chromatographic separation was achieved on Waters Atlantis dC18 (4.6 X 150mm) column with a mobile phase consisting of 0.033M phosphate buffer and methanol (35:65). The mobile phase was filtered using an organic filter paper and sonicated for about 20 min. The flow rate was 1ml/min and 242nm wavelength was used for detection. Force degradation studies were conducted under three conditions namely; acidic, basic and hydroxide peroxide conditions. With the HPLC linearity concentration was in the range of 5-80μg/ml with a correlation coefficient (R2) of 0.9995. There was no interference with drug carriers. The suggested reverse phase HPLC methodology is simple, selective, linear and robust in quantifying the amount of CAR in the various solid dispersion samples. In hydrogen peroxide a degraded product was found on the chromatogram unlike that of the acidic and basic conditions. Degradation occurred more strongly in the acidic condition than in the basic condition. The binary systems were less stable than the ternary system solid dispersions due to the presence of HP-β-CD.
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