PubMed · 4325293
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H Prydz, A Gladhaug. 1971. Factor X. Immunological studies.. https://pubmed.ncbi.nlm.nih.gov/4325293/
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Adult hens were given oral daily doses of 2 mg (2 microC(i))/kg/day (14% of oral LD(50) in male rats) of [14C]methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate) for 10 consecutive days. Five treated hens were sacrificed at 1, 2, 4, 8, 12, 24, and 48 h after the last dose. Methyl parathion was absorbed from the gastrointestinal tract and distributed rapidly. Maximum radioactivity was detected in tissues within 8 h of dosing, (ng methyl parathion equivalent/g fresh tissue or ml plasma): Plasma (189.2), liver (94.7), kidney (146.2), brain (61.4), gastrointestinal tissues (106.7). Methyl parathion was detected in the plasma, kidney and liver, while methyl parathion metabolite p-nitrophenol was detected in the liver and in the kidney. Elimination of methyl parathion from plasma was monophasic with a terminal half-life of 17.5 h, corresponding to an elimination rate constant of 0.039 ng/hr. Most of the absorbed radioactivity was excreted in the combined fecal-urine excreta (98%). Analysis of the metabolites in the excreta revealed that non-conjugated metabolites accounted for 13% of the total excretion. Conjugated metabolites accounted for 87% of the total excretion; of that, 6% as p-nitrophenyl-glucoronide conjugate, 7% as p-nitrophenyl-sulfate conjugate, 23% as bound hot sulfuric acid hydrolyzable residues, and 51% as water soluble metabolites. The presence of majority of radioactivity in the excreta as conjugated metabolites indicates that determining only unbound p-nitrophenol as a biological marker for methyl parathion exposure underestimates total fecal-urine excretion of p-nitrophenol. The slow elimination rate of methyl parathion is significant, since hens are more comparable to humans with respect to their cytochrome P450 activities.
The interactions of the silane coupling agent methacryloxypropyltrimethoxysilane (MPS) with both fumed silica and a polymethylmethacrylate (PMMA) resin matrix were investigated using thermogravimetric analysis and Fourier transform infrared spectroscopy. OX 50 fumed silica was silanated with MPS at concentrations of 1% and 5% in aqueous ethanol (95%), acetone, and anhydrous toluene. Methyl methacrylate was polymerized with the silanated fumed silica (5% wt/wt) to form composites. The amount of MPS adsorption on the fumed silica and the amount of PMMA attached to the silanated fumed silica were determined by thermogravimetric analysis. MPS could be removed from the fumed silica after washing with methanol, but not after it underwent a drying process at 25 degrees C under vacuum. After vacuum drying at 25 degrees C, two types of adsorbed silane were found, i.e., firmly adsorbed and loosely adsorbed silane. The loosely adsorbed silane could desorb from silica and be incorporated into the polymer matrix through copolymerization with monomeric methyl methacrylate, resulting in crosslinking of the matrix. When the silanated silica was dried at 110 degrees C for 2 h, the loosely adsorbed silane was removed and the amount of firmly adsorbed silane increased. There was a positive correlation between the amount of firmly adsorbed MPS and the amount of PMMA attachment. The highest efficiency for PMMA attachment was found when MPS was adsorbed as a monolayer, because the loosely adsorbed silane did not contribute to the bonding of PMMA, and this suggested that not all of the double bonds of the MPS were accessible for reaction with the methacrylate monomer. Drying at 110 degrees C may also decrease the number of unsaturated double bonds of MPS.
Mucoadhesive, hydroxypropylcellulose (HPC) microspheres were prepared for powder inhalation and their feasibility for enhancing pulmonary drug absorption was investigated. Respirable-sized microspheres, incorporating crystalline or amorphous fluorescein (used as a model drug), were prepared by spray-drying aqueous or ethanol HPC systems, respectively. These were prepared from a variety of HPC grades (SL, L, M and H types) in different fluorescein-HPC ratios (1:1-1:10). The microspheres were administered to tracheally-intubated guinea pigs as powder aerosols and their fluorescein pharmacokinetics studied, and compared to those for pure crystalline fluorescein ('control'). All microspheres were prepared and aerosolized within a MMAD range of 1.3-2.6 microm (GSD< or =2.1). Fluorescein's dissolution was increased in the amorphous form by 6.5-fold when compared to the crystalline material (83.9-87.2 vs. 13.5 microg/ml, respectively). Poor dissolution for the 'control' crystalline fluorescein appeared to be rate-determined, which showed bi-phasic absorption profiles (T(max)=60 min), simultaneously competing with mucociliary clearance out of the lower airways. While the crystalline/HPC microspheres prolonged absorption, the amorphous fluorescein/HPC microspheres showed rapid absorption with T(max)=0 min (immediately after the administration had terminated). This was explained by enhanced fluorescein dissolution and was consistently observed irrespective of the fluorescein-HPC ratio or HPC grade. However, the microspheres with the least viscous HPC-SL and the lowest fluorescein-HPC ratio (1:1) failed to enhance bioavailability, presumably because the mucociliary clearance was undisturbed. In contrast, the microspheres with the highly viscous HPC-H with ratios > or = 1:4 successfully enhanced absorption, achieving 88.0% bioavailability by virtue of HPC increasing the dissolution and retarding the mucociliary clearance.