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Timing of food intake has a marked effect on the bioavailability of clodronate.

Because of the low and variable bioavailability of bisphosphonates and the huge effect of food on their gastrointestinal absorption, it is of utmost importance to know the optimal timing of drug intake in relation to food intake. We investigated the effect of time on the bioavailability of clodronate when the drug was administered 2, 1, or 0.5 h before breakfast, with breakfast, or 2 h after breakfast (in the middle of a 4-h fast). The study was conducted as a single-center, open, balanced, randomized, crossover pharmacokinetic study in 31 healthy subjects aged 21 to 34 years. The volunteers participated in five different sessions with 800 mg of oral clodronate, and these sessions were separated by washout phases, each for at least 1 week. The primary pharmacokinetic variables were the area under the serum concentration time curve in 24 h (AUC(0-24)) for clodronate and the maximal concentration of clodronate in serum (C(max)). Clodronate was absorbed rather similarly when taken in the morning on an empty stomach 2, 1, or 0.5 h before breakfast, but because the best absorption occurred (as expected) when the drug was taken 2 h before breakfast, this scheme served as the reference treatment. As evaluated by area under the serum concentration time curves, the dose-breakfast interval of 1 h scarcely reduced absorption from the reference treatment level (relative absorption 91%, p = 1.0). Compared with the reference treatment, clodronate was absorbed with 69% efficacy (p = 0.65) when breakfast followed only 0.5 h later. The dose-breakfast intervals of 0.5 and 1 h did not differ significantly from each other (p = 0.85). Absorption was, however, only 34% (p < 0.0001) of the optimum when the drug was taken 2 h after breakfast, and only 10% of optimal when clodronate was taken with breakfast (p < 0.0001). In conclusion, it can be recommended to take Bonefos capsules in the morning on an empty stomach at least 0.5 h before breakfast.

Adult↗

Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in men.

The present study examined whether replacing fat with inulin or lupin-kernel fibre influenced palatability, perceptions of satiety, and food intake in thirty-three healthy men (mean age 52 years, BMI 27.4 kg/m(2)), using a within-subject design. On separate occasions, after fasting overnight, the participants consumed a breakfast consisting primarily of either a full-fat sausage patty (FFP) or a reduced-fat patty containing inulin (INP) or lupin-kernel fibre (LKP). Breakfast variants were alike in mass, protein and carbohydrate content; however the INP and LKP breakfasts were 36 and 37 % lower in fat and 15 and 17 % lower in energy density respectively compared with the FFP breakfast. The participants rated their satiety before breakfast then evaluated patty acceptability. Satiety was rated immediately after consuming the breakfast, then over the subsequent 4.5 h whilst fasting. Food consumed until the end of the following day was recorded. All patties were rated above 'neither acceptable or unacceptable', however the INP rated lower for general acceptability (P=0.039) and the LKP lower for flavour (P=0.023) than the FFP. The LKP breakfast rated more satiating than the INP (P=0.010) and FFP (P=0.016) breakfasts. Total fat intake was 18 g lower on the day of the INP (P=0.035) and 26 g lower on the day of the LKP breakfast (P=0.013) than the FFP breakfast day. Energy intake was lower (1521 kJ) only on the day of the INP breakfast (P=0.039). Both inulin and lupin-kernel fibre appear to have potential as fat replacers in meat products and for reducing fat and energy intake in men.

Adult↗

Perceptions and reasons for choice of fat- and fibre-containing foods by Swedish schoolchildren.

This study investigated schoolchildren's breakfast choices focusing on their reported usual intake and perceptions of fat-reduced or fibre-enriched alternatives. A total of 184 eleven- to fifteen-year-old were asked to participate, and 181 completed the study. Using pictures of food items, the children were instructed to reproduce their usual breakfast, and then breakfasts that would be: healthy, tasty, consumed by their parents, or approved by their parents. Participants' usual breakfast included breads and breakfast cereals containing a higher fibre content than that of the breakfast reported as most palatable. Their usual breakfast also contained products with less fibre than was the case for their healthy or perceived parental norm breakfasts. This may be interpreted as evidence that high-fibre bread and breakfast cereals are perceived as healthy but that consumption of these products is limited by palatability. In contrast to the ambivalence towards cereal products, corresponding disagreements between breakfasts were not observed for milk, and only a small systematic disagreement was observed for spread. Thus, the majority consumed the kind of milk and spread perceived as being healthy, tasty and parentally sanctioned despite the fact that full-fat products were frequently consumed. In conclusion, the results suggest that taste may be a barrier to consumption of high-fibre products, while consumption of low-fat products appears to be impeded by health beliefs.

Adolescent↗

Effect of meal sequence on postprandial lipid, glucose and insulin responses in young men.

OBJECTIVE: To investigate whether the postprandial changes in plasma triacylglycerol (TAG), nonesterified fatty acids (NEFA), glucose and insulin concentrations in young men were the same if an identical meal was fed at breakfast and lunch, and if the response to lunch was modified by consumption of breakfast. METHODS: In two trials (1 and 2) healthy subjects (age 22+/-1 y, body mass index 22+/-2 kg/m(2)) were fed the same mixed macronutrient meal at breakfast at 08:00 h and lunch at 14:00 h. In the third trial, no breakfast was fed and the overnight fast extended until lunch at 14:00 h. Addition of [1,1,1-(13)C]tripalmitin to one meal in each trial was used to distinguish between endogenous and meal-derived lipids. RESULTS: The postprandial changes in TAG, NEFA and glucose concentrations were similar in trials 1 and 2. The change in plasma total TAG concentration was about two fold less (P<0.05) after lunch compared to breakfast. Postprandial NEFA suppression was the same after breakfast and lunch. Glucose and insulin responses were significantly greater following lunch suggesting decreasing insulin sensitivity during the day. Consumption of breakfast did not alter the postprandial total TAG or NEFA responses after lunch. Measurement of [(13)C]palmitic acid concentration showed that handling of TAG and NEFA from the meal was the same after breakfast and lunch, and was not altered by consumption of breakfast. CONCLUSIONS: Overall, these data suggest that in young, healthy men regulation of plasma TAG from endogenous sources, principally VLDL, but not chylomicrons during the postprandial period leads to differences in the magnitude of lipaemic response when the same meal was consumed at breakfast or at lunch 6 h later.

Adult↗

Clinical trial of risedronate in Japanese volunteers: a study on the effects of timing of dosing on absorption.

Because of its chemical structure, risedronate was thought to form a complex with divalent cations, e.g., Ca(2+), and to be likely to show changes in the efficiency of absorbance from the gastrointestinal tract according to the presence of food. Therefore, we conducted a crossover study using healthy Japanese adults to examine the effects of food intake on absorption after the oral administration of risedronate and to choose the best timing of regimen for risedronate. Using single doses of 5 mg risedronate, the following four dose times were investigated: (a) in the morning under a fasting condition without breakfast; (b) 30 min before breakfast; (c) 30 min after breakfast; and (d) 3 h after breakfast. The results showed that the C(max) and AUC(0-24) of the plasma risedronate concentrations and its cumulative urinary excretions decreased in the following order: fasting without breakfast >>30 min before breakfast >>3 h after breakfast >>30 min after breakfast. In other words, it was demonstrated that the absorption of risedronate decreases due to the effects of food. Several adverse events, whose causality with risedronate was unknown or possibly related, were observed, including headaches, diarrhea, increased CK-BB, and an increased urinary Beta(2)-microglobulin excretion rate, but none of these events was clinically significant, and none differed in frequency or severity from the events after a single oral administration. In consideration of the optimal practical timings required to administer risedronate for Japanese patients, therefore, it was found that ingesting the drug immediately after waking up in the morning, when the stomach is empty, was optimal, and that it was necessary to refrain from eating and drinking for at least 30 min after drug ingestion. Therefore, we determined that the optimal time for risedronate to be administered in Japanese patients is 30 min before breakfast.

Administration, Oral↗

Insulin increase in colon cancerogenesis: a case-control study.

BACKGROUND: Our aim was to establish whether individuals who develop colon cancer have elevated blood insulin concentrations. METHODS: This was a case-control study in which 56 normoglycemic patients with colon cancer and a corresponding control group were investigated at the Clinical Hospital Split from April 1998 to April 1999. Data on age, weight, height, and sex of examinees were recorded and concentrations of glucose, insulin, and C-peptide were measured first in the morning before breakfast and again 90 min after breakfast. RESULTS: In the male group of colon cancer patients, we found statistically significant higher blood insulin concentrations 90 min after breakfast (median 34.7 mIU/L, range 3.3-162.6 mIU/L) in comparison to male control group (median 20.7 mIU/L, range 3.1-122.1 mIU/L) (p=0.044). Concentration of C-peptide in blood 90 min after breakfast (median 3.28 nmol/L, range 0.38-6.1 nmol/L) was higher in the male group of colon cancer patients than in male control group (median 1.68 nmol/L, range 0.26-4.26 nmol/L) (p=0.001). No difference was found in concentrations of insulin, C-peptide, and glucose in blood measured in the morning before breakfast between the male group of colon cancer patients and male control group. Ratio of insulin 90 min after breakfast with respect to insulin in the morning before breakfast was higher in the male group of colon cancer patients (median 4.65, range 0.83-22.1) than in male control group (median 1.78, range 0.38-8.75) (p=0.005). Ratio of C-peptide 90 min after breakfast with respect to fasting C-peptide was higher in the male group of colon cancer patients (median 3.22, range 0.74-11.9) than in male control group (median 1.42, range 0.54-6.0) (p=0.001). Women with colon cancer also had statistically significant higher ratio of insulin and C-peptide with respect to female control group. In the female group of colon cancer patients, median for ratio of C-peptide was 2.42 (range 0.43-8.87), while in female control group it was 1.19 (range 0.62-15.4) (p=0.025). Median for ratio of insulin in the female group of colon cancer patients was 4.23 (range 0.25-8.54), while in female control group it was 1.17 (range 0.29-26.89) (p=0.007). CONCLUSIONS: There was a higher increase of insulin 90 min after breakfast in the group of patients with colon cancer than in control group.

Age Factors↗

Iron and folate in fortified cereals.

BACKGROUND: Fortification of cereal-grain products was introduced in 1941 when iron and three vitamins were added to flour and bread. Ready-to-eat cereals were fortified at about the same time. These fortifications have contributed to increased dietary iron intake and reductions in iron deficiency anemia in the US. In 1996, FDA finalized rules for fortification of specific enriched cereal-grain products with folic acid. This measure was instituted to increase the folate intakes of women of child-bearing age and thereby reduce the risk of having a pregnancy affected with a neural tube birth defect. However, with recent increases in fortification, public health officials in the US are concemed that excess intake of specific nutrients such as iron and folic acid may result in toxic manifestations. OBJECTIVE: Our objective was to measure iron and total folate content in breakfast cereals and compare assay to label values for % Daily Value. We also determined by weight the amount of a ready-to-eat breakfast cereal adults would eat and compared this to the labeled serving size, for which the reference amount for this cereal per eating occasion was 1 cup or 30 g. DESIGN: Twenty-nine breakfast cereals were analyzed for iron content using the bathophenanthroline reaction. Twenty-eight cereals were analyzed for total folate, utilizing a microbiological assay with tri-enzyme digestion. Serving size quantities were estimated in seventy-two adults who regularly ate breakfast cereal and were asked to fill a 16 or 22 cm round bowl with the amount of cereal that they would consume for breakfast. RESULTS: When the labeled value was compared to the assayed value for iron content 21 of the 29 breakfast cereals were 120% or more of the label value and 8 cereals were 150% or more of the label value. Overall, analyzed values for iron ranged from 80% to 190% of label values. Analyzed values for folate ranged from 98% to 320% of label values. For 14 of 28 cereals, analyzed values exceeded label declarations by more than 150%. Bran-containing cereals contained the highest amounts of folate relative to their label declarations. The median analyzed serving size for the breakfast cereal was 47 g for females, 61 g for males with a combined median of 56 g as compared to the label value of 30 g. CONCLUSIONS: Analyzed values of iron and folic acid in breakfast cereals were considerably higher than labeled values. For adults, the amount of cereal actually consumed was approximately 200% of the labeled serving size. When the quantity of cereal consumed is more than the labeled serving size and when the levels of iron and folate are higher than declared, the intake of both will be significantly greater than the labeled values. It will be important to continue monitoring serum ferritin and folate levels in NHANES IV, since daily consumption of breakfast cereals may contribute to excessive intakes of iron and folate.

Edible Grain↗

Effect of prefeeding lipid on food intake and satiety in man.

Experiments were carried out in normal volunteers to investigate whether preingestion of lipid reduces food intake. In the first set of experiments, 300 ml beef consomme soup with or without 60 g margarine was fed to each of six volunteers, followed 20 minutes later by either a low fat solid meal or a preselected appetising meal. Subjects were allowed to eat as much of the meal as they wished. Preingestion of the high fat soup had no significant effect on the consumption of either of the solid meals and did not influence sensations of hunger or fullness. As we have previously shown that prefeeding a fatty soup delays gastric emptying of a subsequent meal, this suggests that gastric distension may play a relatively minor role in regulating food intake. In the second set of experiments, we studied the effect of ingesting either a high fat breakfast (65 g fat, 927 kcal) or a similar low fat breakfast (8-1 g fat, 418 kcal) on the consumption of a preselected appetising lunch in six healthy volunteers. The high fat breakfast significantly reduced the amount of the meal eaten at lunchtime (p less than 0.02), the total energy intake from the meal (p less than 0.05) and the rate of eating (p less than 0.05) compared with the low fat breakfast. When the subjects were presented with their lunchtime meal they felt significantly less hungry after the high fat breakfast (p less than 0.05). Only a small proportion of either meal (15% of the high fat meal v 12% of the low fat meal) remained in the stomach and plasma glucose concentrations had returned to fasting levels. Plasma triglyceride concentrations were much higher at lunchtime after ingestion of the high fat breakfast (p<0.001). The energy intake from the breakfast and lunch combined was not significantly different on the high fat breakfast day, indicating that the energy consumption at lunch compensates for the amount eaten at breakfast. These results are compatible with the concept that the interaction of nutrients with small intestinal receptors may play a part in limiting food intake.

Blood Glucose↗

[Gastric emptying rate in healthy subjects and patients (a radionuclide study)].

The authors proposed a method for the determination of differences in the rate of evacuation of 3 types of test breakfast: boiled semolina, boiled semolina with proteins or fat. Evacuatory function of the gastroduodenal system was investigated in healthy persons and in patients using a gamma-camera. The results obtained have shown that in a majority of healthy persons carbohydrate breakfast was evacuated at the highest rate, breakfast with egg protein was evacuated slower, and breakfast with butter was evacuated even much slower. In duodenal ulcer the rate of evacuation of all 3 types of breakfasts was slowed down, and evacuation was undifferentiated (all 3 types were evacuated at the same slow rate). In patients with liver cirrhosis the evacuation of carbohydrate and protein breakfasts was slow, in calculous cholecystitis these types of breakfasts differed slightly as a result of the slow evacuation of carbohydrate breakfast. The evacuation of breakfast with butter was inhibited almost to the same degree. These results indicate the complex nature of gastric content evacuatory disorders in gastroenterologic patients, and it should be taken into account in differential diagnosis and therapy.

Cholecystitis↗

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time.

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151 +/- 15 min and a lactulose transit time of 86 +/- 22 minutes (X +/- SD, P less than 0.001). The coefficient of variation of breakfast transit time (11.6 +/- 5.3%, range: 6.9-24.2%) was less than that of lactulose transit time (30.7 +/- 7.8%, range: 22.1-50.0%, P less than 0.001). In a second set of experiments, the liquid phase marker (99mTechnetium-diethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3 +/- 5.4) than after the breakfast (33.9 +/- 10.9 min, P less than 0.01) and MCTT was shorter after lactulose (77 +/- 32 vs 104 +/- 40 min, respectively, P less than 0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.

Adult↗

Roles of site and timing of the morning insulin injection in type 1 diabetes.

To investigate the effect of site and timing of insulin injection on post-breakfast plasma glucose concentration, 23 children with type 1 diabetes were given their usual mixture of short- and intermediate-acting insulin five minutes prior to breakfast on one day and between 15 and 60 minutes before breakfast on the alternate day, depending on their 7:00 AM fasting blood glucose concentration. Thirteen children received insulin in an extremity, and 10 in the abdominal wall. Plasma insulin and glucose patterns were similar for the two injection sites. The mean post-breakfast peak glucose increment was significantly lower and the mean increment in free insulin values during the first hour after breakfast was higher on the day when insulin preceded breakfast by 30 to 60 minutes. Thus, significant reductions in post-breakfast hyperglycemia can be achieved by increasing the interval between the injection and breakfast in proportion to the fasting capillary glucose concentration. The timing of the morning insulin injection may be more important than the injection site.

Adolescent↗

Initial treatment of the young hypertensive: thiazide diuretic or beta-adrenoreceptor-blocking agent in a single daily dose?

1. Nine men aged 20-33 years with essential hypertension measured their own blood pressure at home, lying and standing, three times daily, under conditions of everyday living. The last 14 days' readings (eighty-four observations) from control and treatment periods of at least 4 weeks' duration were used to calculate mean pressures. 2. In eight patients, propranolol (40 mg thrice daily with meals) significantly lowered "mean blood pressure" (diastolic+1/3[systolic-diastolic]) but methyclothiazide (5 mg with breakfast) did not. In five subjects, prindolol (5 mg thrice daily with meals) significantly lowered "mean blood pressure" but methyclothiazide (5 mg with breakfast) did not. 3. In six subjects there was no significant difference between "mean blood pressure" when taking propranolol doses 120 mg with breakfast, 60 mg with breakfast and with the evening meal, and 40 mg with each meal. In five subjects there was no significant difference between "mean blood pressure" when taking metoprolol 200 mg with breakfast and 100 mg with breakfast and with the evening meal. In four subjects there was no significant difference between "mean blood pressure" when taking prindolol 30 mg with breakfast, 15 mg with breakfast and with the evening meal, and 10 mg with each meal. 4. In young males with essential hypertension, beta-adrenoreceptor blockers were more effective than a thiazide diuretic in lowering blood pressure, and were effective in a single daily dose.

Adrenergic beta-Antagonists↗

The National Evaluation of School Nutrition Programs: program impact on dietary intake.

This article describes the dietary analysis component of the National Evaluation of School Nutrition Programs. It addresses two research questions: 1) do participants and nonparticipants in the school nutrition programs have different calorie and nutrient intakes for 24 h, breakfast, and/or lunch and 2) if there are differences in the nutritional quality or total quantity of food consumed? Students who participate in the School Lunch Program get more than nonparticipants of almost all nutrients that were examined, both at lunch and during 24 h. The superior lunch and 24-h intakes of Lunch Program participants are due to the higher nutritional quality of the School Lunch compared with lunches that nonparticipants eat. The most important impact of the School Breakfast is that when the program is available, it increases the likelihood that children will eat breakfast, and children who eat breakfast have significantly higher intakes of nutrients than children who skip breakfast. The School Breakfast provides more calcium, phosphorus, protein, and magnesium than a non-US Department of Agriculture breakfast, but less vitamin A, vitamin B6, niacin, thiamin, and iron. The positive impacts of calcium and phosphorus carry over 24 h, while the negative impacts for vitamin A, vitamin B6, niacin, thiamin, and iron are made up during the remainder of the day. Although strong conclusions cannot be drawn about the impact of the Milk Program, milk is an important component of all US Department of Agriculture school nutrition programs and makes a major contribution to student dietary intake. Its presence in the meal patterns probably accounts for some of the greater nutrient intakes associated with participation in the School Lunch Program and most of the greater intakes associated with participation in the School Breakfast Program.

Adolescent↗

Gut delivery of budesonide, a locally active corticosteroid, from plain and controlled-release capsules.

OBJECTIVE: To compare the pharmacokinetics and site of uptake of budesonide from a controlled-release formulation and a deuterium-labelled standard formulation given before and after a meal. METHODS: Six healthy volunteers were randomized into an open, crossover study. They received 4.5 mg controlled-release budesonide (mixed with In pellets to trace gastrointestinal transit) and 4.8 mg 2H8-budesonide simultaneously at each of two visits: one visit before a standardized breakfast and the other after breakfast. Plasma concentrations of budesonide were followed over 24 h. The transit of the (111)In pellets through the gastrointestinal tract was followed for 36 h. Data on the site of absorption were calculated from transit times and absorption curves. RESULTS: The time to peak plasma concentration was significantly increased with controlled-release budesonide when compared with the deuterium-labelled standard formulation (before breakfast, 4.5 h vs 1.8 h; after breakfast, 5.2 h vs 2.9 h). When given after breakfast, the controlled-release formulation was associated with a mean residence time 1.6 h longer than that seen with the standard formulation. However, the areas under the plasma concentration curves were similar with the two formulations, regardless of when the treatments were given (before breakfast, 18.0 +/- 3.8 nmol/l vs 18.0 +/- 6.0 nmol/l; after breakfast, 16.9 +/- 7.0 nmol/l vs 18.5 +/- 9.0 nmol/l). Over 60% of the total budesonide absorbed from controlled-release capsules was delivered and absorbed in the ileum and colon. The corresponding proportion for the standard formulation was approximately 33%. CONCLUSIONS: Controlled-release budesonide effectively delivers most of the budesonide dose to the ileum and colon, the regions that are most often affected by inflammatory bowel disease. In addition, the time of food intake has little effect on the site of absorption or the bioavailability of the controlled-release formulation. Delivery to the colon and ileum was independent of whether the drug was given before or after breakfast.

Adrenal Cortex Hormones↗

Physiological modulation of plasma free fatty acid concentrations by diet. Metabolic implications in nondiabetic subjects.

OBJECTIVE: To determine the effect of varying the amount of carbohydrate and glycemic index (GI) of breakfast test meals on plasma free fatty acid (FFA) responses of nondiabetic subjects and to see whether the glycemic response at lunch was related to the plasma FFA response to breakfast. RESEARCH DESIGN AND METHODS: We studied eight subjects over a 6-h period on four separate occasions using a randomized Latin-square design. They received isocaloric breakfast test meals that were either high (84 g) or low (41 g) in carbohydrate and had either a high (approximately 100) or a low (approximately 70) GI, followed by a standard lunch 4 h later. RESULTS: The initial fall in plasma FFAs after breakfast was similar for all four test meals, but the extent of rebound differed significantly. The mean plasma FFA concentration just before the start of lunch (4 h) was highest after the low-GI, low-carbohydrate breakfast (418 +/- 42 mumol/l), followed by high-GI, low-carbohydrate (277 +/- 48 mumol/l), high-GI, high carbohydrate (227 +/- 32 mumol/l), and low-GI, high-carbohydrate (149 +/- 23 mumol/l) (P < 0.01). The concentration of plasma FFAs at 4 h was directly related to the total area under the glycemic response curve to lunch (r = 0.691, n = 32, P < 0.0001). CONCLUSIONS: In nondiabetic subjects, the type and amount of carbohydrate eaten at breakfast influences the plasma glucose, insulin, and FFA responses to breakfast and also affects the glucose, insulin, and FFA responses to a subsequent standard lunch. The glycemic responses after lunch were closely related to the plasma FFA concentration 4 h after breakfast, which we speculate is due to the inhibitory effect of FFAs on insulin action.

Adult↗

Limited effect of food composition on the pharmacokinetics of nelfinavir administered twice daily.

UNLABELLED: The objective of the study was to investigate the effect of two different breakfasts on the pharmacokinetics of nelfinavir under steady state conditions. METHODS: Twenty-four healthy male volunteers were evaluated in a 17 days open labeled one sequence crossover study evaluating the effect of a 'light' breakfast (350 kcal) compared to a standard breakfast (800 kcal) on the pharmacokinetics of nelfinavir at steady state during 1250 mg twice daily (BID) administration. RESULTS: After administration with a standard breakfast higher concentrations of nelfinavir were observed during the terminal phase than after administration with a 'light' breakfast. The comparison of the log subset 10 transformed parameters C subset 1-hr-postdose, AUC subset 0-12h, C subset max, and C subset 12 hours, showed that the AUC subset 0-12h was decreased by 13% (P = 0.01) after administration with the 'light' breakfast. Nelfinavir 1250 mg BID was well tolerated. CONCLUSIONS: Although drug intake with a 'light' breakfast' showed a statistically significant decrease for nelfinavir AUC subset 0-12h, this marginal 13% reduction is not considered clinically relevant. No significant effects of the two different breakfasts were found for the remaining three parameters tested C subset 1-hr-postdose, C subset max, and C subset 12 hours.

Adult↗

Meal ingestion provokes entry of lipoproteins containing fat from the previous meal: possible metabolic implications.

BACKGROUND: Prolonged and exaggerated postprandial plasma triacylglycerol (TAG) concentrations are considered as an independent risk factor for coronary artery disease. Western populations eat many meals at regular intervals, and can be in a postprandial state for at least 17 h of a 24 h period. After consuming 2 meals an early plasma TAG peak has been observed after the second meal, the origin of which is unclear. AIM OF THE STUDY: To test the hypothesis that the early TAG peak observed following sequential meals was of intestinal origin and represented fat derived from the previous meal. METHODS: Postprandial plasma lipaemic responses of 17 healthy postmenopausal women were studied by giving a test breakfast followed by a lunch. Watermiscible retinyl palmitate (RP) was added to the breakfast, but not the lunch test meal. Plasma TAG, retinyl esters (RE) and apo B-48 were determined for a 10 h period following breakfast. RESULTS: In response to the test meals, RE, apo B-48 and TAG showed multiple peaks. Despite omission of RP from the lunch, RE showed an early peak response after ingestion of lunch in 15 of 17 subjects. The peak response after lunch of all three markers appeared significantly earlier compared with their respective peak responses after the breakfast (P < 0.0001). The area of RE response after lunch was significantly correlated with the RE lipaemic response to the breakfast (r = 0.67; P < 0.004) and to the fasting TAG concentration (r = 0.48; P < 0.05). CONCLUSIONS: Since the lunch did not contain RP, the distinctive second influx of RE after lunch was believed to have originated from the breakfast. This, together with the fact that all three markers showed an earlier response to the lunch than the breakfast, supports the view that ingestion of a second meal provokes entry of fat from the previous meal, from an as yet unidentified site (gut, enterocytes, lymph). The results indicate that the degree of TAG "storage" from previous meals might be a function of TAG tolerance and provide a possible site of regulation of the entry of fat into the systemic circulation.

Aged↗

Plasma amino acid ratios related to brain serotonin synthesis in response to food intake in bulimia nervosa.

Fifteen bulimic women (BN) and 19 healthy female controls (CO) were studied. The subjects were cross-over treated with either fluoxetine (FXT) or placebo during 4 days. They received, in randomized order, a breakfast containing pure carbohydrate (CHO) or a protein-rich (PROT) breakfast following day 3 and 4 of each treatment period. Twenty-nine different food items were offered for lunch. The fasting serum glucose and insulin concentrations and the fasting plasma tryptophan (Trp)/large neutral amino acid (LNAA) ratio were slightly higher in BN. The changes of these metabolic parameters in response to a CHO or PROT breakfast were similar in both groups. Across breakfast type, the plasma (Trp)/(LNAA) ratio at 120 min after breakfast was higher in BN. Total caloric intake at lunchtime was less in BN. In CO, less carbohydrate was selected at lunchtime following the CHO breakfast, an effect that was abolished by FXT. Breakfast type or FXT did not have any apparent effect on food intake at lunchtime in BN. This might indicate that bulimic subjects are less sensitive to serotoninergic stimuli than control subjects.

Adult↗