Study 1 was registered retrospectively; registration number is NCT03055143, dated February 15, 2017. Study 2 registration number is NCT00862355, dated March 13, 2009.
A novel corticosteroid compound (short form of IUPAC name: SFDAC) has been discovered by Sun Pharma Advanced Research Company (SPARC) Ltd. A randomized, observer-blind, active-controlled, parallel-groups, intranasal multiple escalating dose study was conducted in healthy male subjects to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC formulated as an aqueous suspension for intranasal administration. Intranasal sprays of SFDAC, active control fluticasone propionate (FP) and placebo were administered once in a day for 14 days as per randomization. Various clinical evaluations including 24-hour serum cortisol and urinary free cortisol (UFC) profiles were carried out. Blood samples were collected at pre-defined time-points and analyzed using a validated chromatographic method for estimation of SFDAC and its metabolite. The results of the study indicate that multiple dose of SFDAC intranasal spray upto 3,200 µg is safe and tolerated. Clinically significant suppression of hypothalamic pituitary adrenal (HPA) axis was not observed. The plasma concentration of SFDAC was found to be below the lower limit of quantification (LLQ) at most time-points for all subjects. SFDAC M1 metabolite was detected only at picogram level in plasma. The safety and pharmacokinetic characteristics of SFDAC observed in this study support further clinical development of the SFDAC nasal spray.
Objective: A rapid, selective, sensitive, precise and accurate liquid chromatography in tandem with electro-spray ionization mass spectrometry method has been developed and validated for the simultaneous quantification of bupropion (BPR), hydroxyl bupropion (HBPR), erythrohydrobupropion (EHBPR) and threohydrobupropion (THBPR) in human plasma using only 100µL of human plasma sample. Methodology: Multi reaction monitoring detection was performed by electrospray ionization in the positive ion mode, conferring an additional selectivity to the method. The solid phase extraction technique was used for sample preparation. Chromatographic separation of drug and metabolites with better peak shape and resolution was achieved by using an Acquity BEH phenyl column with an isocratic elution of 42 % methanol and 58 % ammonia (0.06%, v/v) aqueous solution at a flow rate of 0.5 ml/min. Methanol was chosen because it enabled good resolution between THBPR and EHBPR as well as good peak symmetry of all the four analytes. Detection was carried out by mass spectrometry using positive electro-spray ionization mode, and the compounds were monitored using multiple reactions monitoring method. Deuterium-labeled isotopes of the compounds were used as internal standards. Results and Conclusion: No significant matrix effect was observed in the presented method. The assay method was validated over the concentration range of 1.75-500 ng/ml for BPR; 5-1000 ng/ml for HBPR; 0.5-100 ng/ml for EHBPR; and 2-500 ng/ml for THBPR as per FDA guideline and validated method was successfully applied for estimation of drug and metabolite concentration in the healthy adult volunteers, bioequivalence and pharmacokinetic study of Bupropion hydrochloride 300 mg extended release tablets under fasting condition.
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