Physical Stability of Solid Dispersions Containing Triamterene or Temazepam in Polyethylene Glycols

The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 ? PEG 2000 < PEG 4000 ～ PEG 6000.     

DOES LIVER DYSFUNCTION EXPLAIN NEUROPSYCHOLOGICAL STATUS IN RECENTLY DETOXIFIED ALCOHOL-DEPENDENT CLIENTS?

In the search for explanation of persistent cognitive impairmentassociated with alcohol dependence, the possible role of liverdisease has aroused considerable interest. However, review ofthe relevant literature provides only ambiguous support forany general relationship between neuropsycho-logical statusand laboratory tests of liver function. We tested the generalhypothesis, and also two specific hypotheses relating particularliver function parameters (     

The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole

1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800  mg sulphamethoxazole and 160  mg trimethoprim) alone or 1  h after either fluconazole (150  mg) or ketoconazole (200  mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24  h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N₄-acetyl sulphamethoxazole, or sulphamethoxazole N₁-glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points.     

The effect of mutation on linkage disequilibrium

The standard formula for the approach to linkage equilibrium between two diallelic loci, initially at disequilibrium, is expressed in terms of their probability of recombination (Li, 1955). By a simple extension, we show how to incorporate the effects of mutation at one or both loci. It can thereby be inferred that in general these effects are unlikely to be of major importance, contrary to some recent suggestions.     

Parental influences on young girls’ fruit and vegetable, micronutrient, and fat intakes

Objective To evaluate parents’ fruit and vegetable intake and their use of pressure to eat in child feeding as predictors of their 5-year-old daughters’ fruit and vegetable, micronutrient, and fat intakes.Subjects Data were obtained from 191 non-Hispanic white families with 5-year-old girls.Design Parent data included reports of pressure in child feeding and their own fruit and vegetable intake. Girls’ intakes of fruits and vegetables, selected micronutrients, and fat were the main outcomes of interest.Statistical analysis Structural equation modeling was used to test a model describing relationships among parents’ fruit and vegetable intake, parents’ use of pressure in child feeding, and daughters’ fruit and vegetable, micronutrient, and fat intakes.Results The model provided a good fit to the data, revealing that girls’ fruit and vegetable intake was positively related to their parents’ reported fruit and vegetable intake. Parents who consumed fewer fruits and vegetables tended to report greater pressure in child feeding and had daughters who consumed fewer fruits and vegetables. Girls’ reported fruit and vegetable intakes were positively related to their micronutrient intakes and negatively associated with fat intake.Applications/conclusions This research demonstrates that parents’ own fruit and vegetable intake may encourage fruit and vegetable intake in their daughters, leading to higher micronutrient intakes and lower dietary fat intakes. Conversely, pressure to eat may discourage fruit and vegetable intake among young girls. J Am Diet Assoc. 2002;102:58–64.     

Society for Research on Nicotine and Tobacco

The proceedings of the second annual scientific conference of the Society for Research on Nicotine and Tobacco are summarized. The goal of the annual conference was to disseminate information about ongoing nicotine research from biological, behavioral and social perspectives. Data were presented describing our current understanding of the structure and function of neuronal nicotinic acetylcholine receptors, by which nicotine exerts most, if not all, of its effects in the brain. The conformational complexity of receptor subunits expressed in different brain areas contributes significantly to the complexity of responses observed to nicotinic agonists. Nicotine is being developed as a medication that might be used to maintain smoking cessation and to treat various medical diseases. The potential toxicity of nicotine, apart from cigarette smoking, is an important variable in assessing the benefits and risks of such therapeutic applications. The risks of nicotine-containing medications appear to be far less than those associated with tobacco use. Recent data indicate that cigarette smoking is increasing among youth in the United States. Adolescent smokers are interested in quitting and make frequent quit attempts, but are usually not successful. Effective methods are needed to manage adolescent smokers before they become heavily addicted. Nicotine replacement as a pharmacological treatment for smoking cessation has made a significant contribution in improving quit rates. New medications have been developed that target specific populations of smokers.