Effects of feeding 2(3)-tert-butyl 4-hydroxyanisole (BHA) and 3, 5-di-tert-butyl 4-hydroxytoluene (BHT) on the rates of mixed function oxidation and conjugation enzyme reactions have been determined using isolated hepatic microsomal fractions and isolated perfused livers of mice. The treatments with either of the antioxidants have increased the rates of O-demethylation for p-nitroanisole and of O-deethylation for 7-ethoxycoumarin up to 2-fold, both in microsomes and in perfused liver. Analysis of the perfusate showed that the increased amounts of p-nitrophenol and 7-hydroxycoumarin produced by the elevated mixed-function oxidase activities were reflected by the increase in the amounts of glucuronide conjugates and not in the increase for the amounts of the sulfate ester conjugates. Comparison of results also indicated that in the perfused liver, the maximal rate of metabolite conjugation is limited by the maximal rates of the initial mixed function oxidase activities.
Alkylation ; Animal ; Anisoles/metabolism ; Anisoles/pharmacology* ; Butylated Hydroxyanisole/administration & dosage ; Butylated Hydroxyanisole/pharmacology* ; Butylated Hydroxytoluene/administration & dosage ; Butylated Hydroxytoluene/analogs & derivatives* ; Butylated Hydroxytoluene/pharmacology ; Comparative Study ; Coumarins/metabolism ; Female ; Glucuronosyltransferase/metabolism ; Liver/metabolism* ; Mice ; Microsomes, Liver/enzymology ; Microsomes, Liver/metabolism* ; Mixed Function Oxygenases/metabolism ; Oxidation-Reduction ; Perfusion ; Support, U.S. Gov't, P.H.S.

Bioidentical hormone therapy (BHT) refers to the use of hormones that are molecularly and chemically identical to endogenous hormones for purposes of hormone replacement therapy. The specific hormones used in BHT include estrone, estradiol, estriol, progesterone and testosterone. Since the result of the Women's Health Initiative (WHI) trial documented the increased risk of breast cancer, cardiovascular disease and stroke in users of conventional hormone therapy (CHT), use of CHT has declined and there has been increased interest in BHT. Bioidentical hormones have some distinctly different physiologic effects compared with synthetic hormones. Synthetic progestin is associated with an increased risk for breast cancer and cardiovascular disease, while natural progesterone is associated with a decreased risk of breast cancer and cardiovascular disease. Estriol has some unique physiologic effects, which differentiate it from estrone and estradiol. Estriol is associated with a lower risk of breast cancer and would be expected to prevent breast cancer, but few randomized controlled trials have been documented. Some clinical data demonstrate that BHT is associated with a lower risk of breast cancer and cardiovascular disease, and is more efficacious than synthetic hormones. However, there is little evidence in support of this claim. Moreover, estriol has not been approved by the U.S. Food and Drug Administration (FDA). Further studies are needed to confirm the safety and efficacy of BHT.
Breast Neoplasms ; Butylated Hydroxytoluene ; Cardiovascular Diseases ; Estradiol ; Estriol ; Estrone ; Female ; Hormone Replacement Therapy ; Humans ; Menopause ; Progesterone ; Stroke ; Testosterone ; United States Food and Drug Administration ; Women's Health

Bioidentical hormone therapy (BHT) refers to the use of hormones that are molecularly and chemically identical to endogenous hormones for purposes of hormone replacement therapy. The specific hormones used in BHT include estrone, estradiol, estriol, progesterone and testosterone. Since the result of the Women's Health Initiative (WHI) trial documented the increased risk of breast cancer, cardiovascular disease and stroke in users of conventional hormone therapy (CHT), use of CHT has declined and there has been increased interest in BHT. Bioidentical hormones have some distinctly different physiologic effects compared with synthetic hormones. Synthetic progestin is associated with an increased risk for breast cancer and cardiovascular disease, while natural progesterone is associated with a decreased risk of breast cancer and cardiovascular disease. Estriol has some unique physiologic effects, which differentiate it from estrone and estradiol. Estriol is associated with a lower risk of breast cancer and would be expected to prevent breast cancer, but few randomized controlled trials have been documented. Some clinical data demonstrate that BHT is associated with a lower risk of breast cancer and cardiovascular disease, and is more efficacious than synthetic hormones. However, there is little evidence in support of this claim. Moreover, estriol has not been approved by the U.S. Food and Drug Administration (FDA). Further studies are needed to confirm the safety and efficacy of BHT.
Breast Neoplasms ; Butylated Hydroxytoluene ; Cardiovascular Diseases ; Estradiol ; Estriol ; Estrone ; Female ; Hormone Replacement Therapy ; Humans ; Menopause ; Progesterone ; Stroke ; Testosterone ; United States Food and Drug Administration ; Women's Health

With the establishment of HPLC and LC-MS methods to determine the related substances and the content of active pharmaceutical ingredient (API) in ipratropium bromide aerosol products, several packing material-related impurities were identified, including antioxygen BHT and antioxygen 2246. Results showed that these leachable additives from the packing materials may present at a relative high level in the drug solution, and the low content of API in the drug products is usually due to the adsorption of the packing material as well as the leaking of contents. The current available assay methods for the control of ipratropium bromide aerosol products are often lack of specificity and unable to assure the drug quality effectively. To meet the increasing attention on the regulations of drug packing materials, our research would be a pilot study, indicating that the inappropriate packing materials could cause the migration and adsorption of the active ingredients, and the importance to have compatibility studies between packing materials and drugs.
Aerosols ; Antioxidants ; analysis ; Bronchodilator Agents ; administration & dosage ; chemistry ; Butylated Hydroxytoluene ; analysis ; Chromatography, High Pressure Liquid ; Drug Incompatibility ; Drug Packaging ; Ipratropium ; administration & dosage ; chemistry ; Quality Control ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization