Glucagon and insulin response to meals in non-obese and obese Dutch women

Many digestive complaints are associated with abnormalities in gastrointestinal peptide hormone function. To investigate the effect of obesity on the release of pancreatic peptide hormones, we have compared the release of insulin and glucagon in non-obese-obese Dutch women in response to isocaloric mixed meals and to Naloxone, an opioid antagonist. Healthy premenopausal women who were separated into three groups based on body mass index (BMI 28), were fed 600-calorie breakfasts. Higher fasting levels of plasma insulin and glucagon occurred in obese (BMI > 28) than lean (BMI < 23) women, while glucagon and insulin release after a high fat meal occurred in obese women. Naloxone administration in obese women decreased plasma insulin and glucagon, but in lean women, naloxone increased plasma glucagon but did not alter plasma insulin levels. Results indicate differences in opiate effects on pancreatic function in non-obese-obese women

Effect of serotonin re-uptake inhibition by fluoxetine on body weight and spontaneous food choice in obesity

The effect of fluoxetine on body weight and spontaneous food choice was studied in twenty-three healthy, non-depressed, obese females on an outpatient basis. After a one week placebo run-in period, subjects were randomized to receive either fluoxetine (FXT) 60 mg daily (n = 11) or placebo (P) (n = 12) for 6 weeks in a double blind study design. BMI (35.2 +/- 0.8 vs 36.4 +/- 1.3 kg/m2, mean +/- s.e.m.) and age (38.1 +/- 239 vs 37.3 +/- 2.7 years) were not different in either group. No specific diet was prescribed. On four separate days per 14 days food records were collected. Data were analysed with the use of food composition tables. Statistical analysis was performed using Student's t test for independent samples for data on body weight and calorie intake. Macro-nutrient composition of the diet was analysed using multivariate analysis of variance and post hoc Student's t test for independent samples. All subjects lost weight during fluoxetine treatment. Mean (+/- s.e.m.) weight loss in the fluoxetine treated group was 3.6 +/- 0.5 kg, compared to a mean weight gain of 0.3 +/- 0.5 kg in the placebo treated group (P less than 0.001). In all patients food intake was reduced during fluoxetine treatment and this reduction could fully account for the observed weight loss. The mean total caloric intake per day was significantly lower during fluoxetine treatment compared with placebo (FXT 1123 +/- 118 kcal vs P 1845 +/- 87 kcal, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS

Effect of serotonin re-uptake inhibition by fluoxetine on body weight and spontaneous food choice in obesity

The effect of fluoxetine on body weight and spontaneous food choice was studied in twenty-three healthy, non-depressed, obese females on an outpatient basis. After a one week placebo run-in period, subjects were randomized to receive either fluoxetine (FXT) 60 mg daily (n = 11) or placebo (P) (n = 12) for 6 weeks in a double blind study design. BMI (35.2 +/- 0.8 vs 36.4 +/- 1.3 kg/m2, mean +/- s.e.m.) and age (38.1 +/- 239 vs 37.3 +/- 2.7 years) were not different in either group. No specific diet was prescribed. On four separate days per 14 days food records were collected. Data were analysed with the use of food composition tables. Statistical analysis was performed using Student's t test for independent samples for data on body weight and calorie intake. Macro-nutrient composition of the diet was analysed using multivariate analysis of variance and post hoc Student's t test for independent samples. All subjects lost weight during fluoxetine treatment. Mean (+/- s.e.m.) weight loss in the fluoxetine treated group was 3.6 +/- 0.5 kg, compared to a mean weight gain of 0.3 +/- 0.5 kg in the placebo treated group (P less than 0.001). In all patients food intake was reduced during fluoxetine treatment and this reduction could fully account for the observed weight loss. The mean total caloric intake per day was significantly lower during fluoxetine treatment compared with placebo (FXT 1123 +/- 118 kcal vs P 1845 +/- 87 kcal, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)</p

Single dose sublingual testosterone and oral sildenafil versus a dual-route/dual-release fixed-dose combination tablet: a pharmacokinetic comparison

AIM: To compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for Female Sexual Interest/Arousal Disorder. The prototype (formulation 1), consists of a testosterone solution for sublingual administration, and a sildenafil tablet that is administered 2.5 hours later. The dual-route/dual-release fixed-dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner-core of sildenafil with a polymeric time-delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal nonadherence through circumventing the relatively complex temporal dosing scheme. METHODS: 12 healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N-desmethyl-sildenafil. RESULTS: Formulation 2 had a higher maximum concentration (Cmax ) for testosterone, 8.06 ng/ml (95% confidence interval [CI] 6.84-9.28) and higher area under the plasma concentration-time curve (AUC), 7.69 ng*h/mL (95% CI 6.22-9.16) than formulation 1; 5.66 ng/ml (95% CI 4.63-6.69) and 5.12 ng*h/mL (95% CI 4.51-5.73), respectively. Formulation 2 had a lower Cmax for sildenafil, 173 ng/ml (95% CI 126-220) and a lower AUC, 476 ng*h/mL (95% CI 401-551) than formulation 1; 268 ng/ml (95% CI 188-348) and 577 ng*h/mL (95% CI 462-692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40-3.10). CONCLUSIONS: The dual-route/dual-release fixed-dose combination tablet fulfilled its design-criteria and is considered suitable for further clinical testing