Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug–drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin. Therefore, we analyzed seven published microarray datasets, and identified differentially-expressed genes in two inflammatory skin diseases (melanoma and psoriasis). We observed opposite patterns of expression of genes regulating metabolism of specific vitamins and lipids in psoriasis and melanoma samples. Thus, genes controlling the turnover of vitamin D (CYP27B1, CYP24A1), vitamin A (ALDH1A3, AKR1B10), and cholesterol (CYP7B1), were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1). Genes controlling abnormal keratinocyte differentiation and epidermal barrier function (CYP4F22, SULT2B1) were up-regulated in psoriasis. The up-regulated CYP24A1, CYP4F22, SULT2B1, and CYP7B1 genes are potential drug targets in psoriatic skin. Both disease samples showed diminished drug metabolizing capacity due to downregulation of the CYP1B1 and CYP3A5 genes. However, melanomas showed greater loss of drug metabolizing capacity due to downregulation of the CYP3A4 gene.

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Aim and objectives: Among the various SSRI and 5-HT-1A, partial agonist vilazodone is one of them. It has antidepressant and anti-anxiety activities. This method's main aim and the objective was to develop and validate a bio-analytical method of Vilazodone in human plasma by LC-MS/MS (API-4000) and its application to estimate pharmacokinetics. Method: For reporting this investigation, Analyst software, 1.6.3 used. The mobile phase was acetonitrile with 0.1% formic acid as an organic solvent and Milli Q water with 10Mm ammonium acetate and 0.1% formic acid using the gradation method 7.0min run time. The calibration standard concentrations were 1.0 to 64 ng/ml. Plasma precipitation was by protein precipitation technique. Result: The accuracy of calibration concentrations of Vilazodone was 93.5-104.39% and stability study showed 96.41-106.71%, 94.77-96.36%, 92.22-101.38%, 94.15-98.47%, 93.95-95.75% remaining for freeze-thaw, short term, long term, benchtop and autosampler stability respectively. Recovery was to be 98.10-98.99%; the matrix factor was 0.94-0.96. The maximum plasma concentration of reference preparation was 13.445±2.842ng/ml (Cmax) at a time 6.792±0.846hr. (Tmax). The maximum plasma concentration of test preparation was 13.218±3.231ng/ml (Cmax) at a time 6.958±0.793hr (Tmax) The relative bioavailability of the test preparation was to be 94.66 % of that of the reference preparation. Conclusion: The present investigation was highly selective, sensitive, reproducible, low matrix effect, high recovery and low time-consuming method. It was validated as per USFDA and EMA guideline and successfully used in comparative pharmacokinetics.

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