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.     

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.     

A KELLOGG FOUNDATION INITIATIVE: COMMUNITY PARTNERSHIPS — SOUTH AFRICA

Health personnel education in South Africa is currently directed towards preparation for work in tertiary care settings, is highly specialized, and segmented racially. The majority of South Africans are in desperate need of primary health care services. In preparing for transition to a future South Africa, a community-partnership effort is in its initial stages to redress this imbalance.     

TEENAGE HEAVY DRINKERS: ALCOHOL-RELATED KNOWLEDGE, BELIEFS, EXPERIENCES, MOTIVATION AND THE SOCIAL CONTEXT OF DRINKING

During 1988 and 1989 a survey was conducted of the drinkinghabits and alcohol-related beliefs of a national sample of teenagersin England. Data were obtained from 6,244 respondents virtuallyall aged 14–16. Heavy drinkers were significantly morelikely to report drinking in a mixed sex group than were otherteenagers. They were also more likely than others to have drunkillegally in licensed premises, and were distinctive from otherteenagers in relation to their self-reported reasons for drinkingand their alcohol-related beliefs.     

Change in Nutrient Intakes, Number of Servings, and Contributions of Total Fat from Food Groups in 4- to 10-Year-Old Children Enrolled in a Nutrition Education Study

Objective To determine change in nutrient intakes, number of servings, and contributions of total fat from food groups in children who lowered their dietary fat intake.Design A research and demonstration study designed to lower plasma low-density lipoprotein cholesterol level. There were four study groups: two intervention and two control groups. All children had hypercholesterolemia except for those in one control group. Three 24-hour dietary recalls were collected on randomly assigned days over a 2-week period at baseline and 3 months after the intervention.Subjects Three hundred three 4- to 10-year old children from suburbs north of Philadelphia, Pa.Interventions One intervention involved a home-based, parent-child autotutorial program (PCAT group) with audiotaped stories and print materials for the children and their families; the other intervention involved one face-to-face counseling session with a registered dietitian (counseling group).Outcome measures Change in mean nutrient intakes compared with the Recommended Dietary Allowance (RDA); change in number of servings and mean grams of total fat contributed from 10 different food groups.Statistical analyses performed Analyses of variance and χ² analyses.Results Children in every study group had mean intakes of all nutrients (except vitamin D) greater than 67% of the RDA 3 months after the baseline measurement. Several food groups (ie, meats, dairy products, fats/oils, and desserts) provided less total fat to the diets of children who reduced their dietary lipid intake after 3 months (ie, PCAT and counseling groups). These children also reduced the mean number of servings selected from these food groups. Within these same food groups, some children consumed fewer servings of higher fat foods and more servings of lower fat foods.Applications/conclusions Children who lowered their dietary fat intake after intervention reported both quantitative and qualitative changes in food choices from several food groups. These choices did not significantly reduce their nutrient intakes. J Am Diet Assoc. 1996; 96:865-873.