Pharmacokinetics of oseltamivir phosphate and oseltamivir carboxylate in non-pregnant and pregnant rhesus monkeys.

Oseltamivir is an antiviral drug approved to treat influenza in humans. Although the dosing regimen of this drug is well established for non-pregnant patients, it is not clear if the significant physiological alterations associated with pregnancy affect the pharmacokinetics of oseltamivir and, thus, warrant different dosing regimens to assure efficacy. In this study, we investigated the suitability of rhesus macaques as an animal model for studying oseltamivir pharmacokinetics during all trimesters of pregnancy in comparison to pre-pregnant conditions.

Use of a physiologically-based pharmacokinetic model to explore the potential disparity in nicotine disposition between adult and adolescent nonhuman primates.

The widespread use and high abuse liability of tobacco products has received considerable public health attention, in particular for youth, who are vulnerable to nicotine addiction. In this study, adult and adolescent squirrel monkeys were used to evaluate age-related metabolism and pharmacokinetics of nicotine after intravenous administration. A physiologically-based pharmacokinetic (PBPK) model was created to characterize the pharmacokinetic behaviors of nicotine and its metabolites, cotinine, trans-3'-hydroxycotinine (3'-OH cotinine), and trans-3'-hydroxycotinine glucuronide (3'-OH cotinine glucuronide) for both adult and adolescent squirrel monkeys.

Developmental neurotoxicity of inorganic arsenic exposure in Sprague-Dawley rats.

High levels of inorganic arsenic (iAs) exposure are associated with severe health effects. Less clear are effects of lower exposure levels on neurodevelopment. Relative to maternal intake, there is limited lactational transfer of arsenic in humans or rodents, yet there are few rodent studies which directly exposed preweaning animals.

Effects of human sulfotransferases on the cytotoxicity of 12-hydroxynevirapine.

Nevirapine, a non-nucleoside reverse transcriptase inhibitor used for the treatment of AIDS, can cause serious skin rashes and hepatotoxicity. Previous studies have indicated that the benzylic sulfate 12-sulfoxynevirapine, the formation of which is catalyzed by human sulfotransferases (SULTs), may play a causative role in these toxicities. To characterize better the role of 12-sulfoxynevirapine in nevirapine-induced cytotoxicity, the ability of 12 expressed human SULT isoforms to conjugate 12-hydroxynevirapine was assessed.

A simple and highly sensitive UPLC-ESI-MS/MS method for the simultaneous quantification of nicotine, cotinine, and the tobacco-specific carcinogens N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in serum samples.

According to the World Health Organization, the consumption of tobacco products is the single largest cause of preventable deaths in the world, exceeding the total aggregated number of deaths caused by diseases such as AIDS, tuberculosis, and malaria. An important element in the evaluation of the health risks associated with the consumption of tobacco products is the assessment of the internal exposure to the tobacco constituents responsible for their addictive (e.g.

Cytochrome P450-mediated metabolism of triclosan attenuates its cytotoxicity in hepatic cells.

Triclosan is a widely used broad-spectrum anti-bacterial agent. The objectives of this study were to identify which cytochrome P450 (CYP) isoforms metabolize triclosan and to examine the effects of CYP-mediated metabolism on triclosan-induced cytotoxicity. A panel of HepG2-derived cell lines was established, each of which overexpressed a single CYP isoform, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP4A11, and CYP4B1.

Timing and route of exposure affects crystal formation in melamine and cyanuric exposed male and female rats: gavage vs. feeding.

Effects of the dosing matrix and timing on the onset of renal crystal formation were evaluated in male and non-pregnant female rats (Fisher 344) exposed to both melamine (MEL) and cyanuric acid (CYA) for 28 days. Rats were fed ground feed containing 60 ppm MEL and 60 ppm CYA, (5 mg/kg bw/day equivalent), or exposed via oral gavage to carboxymethylcellulose containing 5 mg/kg bw MEL followed by 5 mg/kg bw CYA either consecutively (<1 min apart) or delayed 45 min after MEL. Staggered gavage exposure to MEL/CYA caused extensive renal crystal formation as compared to when the two compounds were administered consecutively or in feed.

Cyclofructan 6 based stationary phases for hydrophilic interaction liquid chromatography.

New stationary phases for hydrophilic interaction liquid chromatography (HILIC) were synthesized by covalently attaching native cyclofructan 6 (CF6) to silica gel. The chromatographic characteristics of the new stationary phases were evaluated and compared to three different types of commercial HILIC columns. The CF6 columns produced considerably different retention and selectivity patterns for various classes of polar analytes, including nucleic acid compounds, xanthines, β-blockers, salicylic acid and its derivatives, and maltooligosaccharides.

Comparison of HPLC enantioseparation of substituted binaphthyls on CD-, polysaccharide- and synthetic polymer-based chiral stationary phases.

Retention and enantioseparation behavior of ten 2,2'-disubstituted or 2,3,2'-trisubstituted 1,1'-binaphthyls and 8,3'-disubstituted 1,2'-binaphthyls, which are used as catalysts in asymmetric synthesis, was investigated on eight chiral stationary phases (CSPs) based on beta-CD, polysaccharides (tris(3,5-dimethylphenylcarbamate) cellulose or amylose CSPs) and new synthetic polymers (trans-1,2-diamino-cyclohexane, trans-1,2-diphenylethylenediamine and trans-9,10-dihydro-9,10-ethanoanthracene-(11S,12S)-11,12-dicarboxylic acid CSPs). Normal-, reversed-phase and polar-organic separation modes were employed. The effect of the mobile phase composition was examined.

Analysis for estrogens as environmental pollutants--a review.

The approaches to the analysis for estrogen compounds as environmental pollutants are critically reviewed and evaluated on the basis of significant, recent original publications. The importance of sample pretreatment and analyte preconcentration techniques is pointed out, with an emphasis on SPE and on the use of highly selective interactions such as molecular recognition. The hyphenated systems of high-performance gas or liquid chromatography and mass spectrometric techniques are discussed as the basic methods of determination of estrogens in environmental samples.

Cellulose tris(3,5-dimethylphenylcarbamate)-based chiral stationary phases as effective tools for enantioselective HPLC separation of structurally different disubstituted binaphthyls.

Cellulose tris(3,5-dimethylphenylcarbamate)-based chiral stationary phases (CSPs) were used for a study of the HPLC retention and enantioseparation behavior of 2,2'-disubstituted or 3,2,2'-trisubstituted 1,1'-binaphthyls and 8,3'-disubstituted 1,2'-binaphthyls. The effects of the mobile phase composition in normal- (NP) and reversed-phase (RP) separation modes were investigated. The NP mobile phases contained n-hexane and propane-2-ol at various volume ratios, the RP ones were obtained by mixing acetonitrile with water or a 20 mM phosphate buffer of pH 6.