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Browsing by Author "Patil, Avinash"
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Item Characterization of Maternal and Fetal CYP3A-Mediated Progesterone Metabolism(Taylor & Francis, 2017-10) Quinney, Sara K.; Benjamin, Tara D.; Zheng, Xiaomei; Patil, Avinash; Obstetrics and Gynecology, School of MedicineINTRODUCTION: Progesterone is critical for maintaining pregnancy and onset of labor. We evaluated CYP450-mediated progesterone meta-bolism, specifically the contribution of CYP3A isoforms. MATERIALS AND METHODS: In vitro progesterone metabolism was characterized in human liver microsomes (HLMs) with and without selective cytochrome P450 inhibitors and in recombinant CYP3A4, CYP3A5, and CYP3A7. 6β-hydroxyprogesterone (6β-OHP) and 16α-hydroxyprogesterone (16α-OHP) metabolites were quantified by HPLC/UV and fit to the Michaelis-Menten equation to determine Km and Vmax. The effect of CYP3A5 expression on progesterone clearance was determined by in vitro in vivo extrapolation. RESULTS: Ketoconazole inhibited formation of both 6β-OHP and 16α-OHP more than 95%. 6β-OHP and 16α-OHP were both produced by CYP3A4 (2.3 and 1.3 µL/min/pmol, respectively) to a greater extent than by CYP3A5 (0.09 and 0.003 µL/min/pmol) and CYP3A7 (0.004 and 0.003 µL/min/pmol). CONCLUSIONS: Maternal clearance of progesterone by hepatic CYP450's is driven primarily by CYP3A4, with limited contributions from CYP3A5 and CYP3A7.Item A randomised bite force study assessing two currently marketed denture adhesive products compared with no‐adhesive control(Wiley, 2019-06) Varghese, Roshan; Burnett, Gary R.; Souverain, Audrey; Patil, Avinash; Gossweiler, Ana G.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryUnlike other oral care products, there are limited technologies in the denture adhesive category with the majority based on polymethyl vinyl ether/maleic anhydride (PVM/MA) polymer. Carbomer‐based denture adhesives are less well studied, and there are few clinical studies directly comparing performance of denture adhesives based on different technologies. This single‐centre, randomised, three‐treatment, three‐period, examiner‐blind, crossover study compared a carbomer‐based denture adhesive (Test adhesive) with a PVM/MA‐based adhesive (Reference adhesive) and no adhesive using incisal bite force measurements (area over baseline over 12 hr; AOB0–12) in participants with a well‐made and at least moderately well‐fitting complete maxillary denture. Eligible participants were randomised to a treatment sequence and bit on a force transducer with increasing force until their maxillary denture dislodged. This procedure was performed prior to treatment application (baseline) and at 0.5, 1, 3, 6, 9, and 12 hr following application. Forty‐four participants were included in the modified intent‐to‐treat population. AOB0–12 favoured both Test adhesive to No adhesive (difference: 2.12 lbs; 95% CI [1.25, 3.00]; p < 0.0001) and Reference adhesive to No adhesive (difference: 2.76 lbs; 95% CI [1.89, 3.63]; p < 0.0001). There was a numerical difference in AOB0–12 for Test versus Reference adhesive (−0.63 lbs; [−1.51, 0.25]); however, this was not statistically significant (p = 0.1555). Treatments were generally well tolerated. Both PVM/MA and carbomer‐based denture adhesives demonstrated statistically significantly superior denture retention compared with no adhesive over 12 hr, with no statistically significant difference between adhesives.