Cisapride increases peak plasma and saliva ethanol levels under fasting conditions

Abstract. Dziekan G, Contesse J, Werth B, Schwarzer G. Keinhart WH (Kantonsspital, Chur, Switzerland and University of Freiburg, Freiburg, Germany). Cisapride increases peak plasma and saliva ethanol levels under fasting conditions. J Intern Med 1997; 242: 479-482.
Objectives: Alcohol absorption is influenced by gastric first-pass metabolism through an alcohol dehydrogenase and the gastric emptying time. Whilst an influence of antisecretory drugs and aspirin on gastric alcohol metabolism has been described, the role of prokinetic drugs has not been determined.
Design: A randomized, placebo-controlled doubleblind cross-over study was performed.
Setting: Out-patient facilities of a referral hospital.
Subjects: Eight male volunteers (age range 25–46 years).
Intervention: Treatment with two doses of either placebo or cisapride 150 pgkg 7 h and 20 min before drinking 0.5 g/kg alcohol either in a fasting state or during a standardized meal (12 kcalkg).Main outcome measures. Plasma and saliva ethanol concentrations were measured during 4 h. Results. Cisapride increased peak plasma ethanol levels in fasting subjects from 15.6 (SD 1.4, 95'%-KI 14.7i16.6) to 17.8 (SD 2.7, 9SYo-KI 15.9i19.7)mmol/L and saliva ethanol 30 min after alcohol ingestion from 11.4 (SD 2.2, 95%-KI 9.9;12.9) to 15.9 (SD 4.3, 95Yo-KI 12.9;18.8) mmol/L. A significant interaction between fasting state and drug intake was found for the 30 min saliva ethanol values (P < 0.05, ANOVA for repeated measurements).
Conclusions: Cisapride may increase ethanol levels under fasting conditions. Patients treated with prokinetic drugs should be informed about this possibility.     

Effect of moderate white wine consumption on serum IgA and plasma insulin under fasting conditions

BACKGROUND/AIMS: The present study aims to investigate the contribution of alcohol toxicity to the development of malnutrition by assessing the effect of consuming a moderate amount of white wine on plasma insulin and serum IgA under fasting conditions. METHODS: A total of 5 non-alcoholic males aged between 19 and 22 years participated in the current investigation. The experimental procedure required participants to undergo a 6-hour fast before ingesting 4 standard units of alcohol (40 g) in the form of white wine over a 120-min period. The level of blood alcohol, plasma insulin and serum IgA was assessed at 30-min intervals across the 120-min experimental period. RESULTS: Consuming alcohol promotes a significant increase in serum IgA in the absence of any change in plasma insulin or ketone production in fasted individuals. CONCLUSION: White wine prior to a meal does not promote glucose metabolism and utilization and may increase the risk of developing a transient diabetic condition due to an alteration in energy metabolism.     

Effect of food and antacids on the pharmacokinetics of pirfenidone in older healthy adults

Pirfenidone is a small, synthetic molecule under investigation for treatment of idiopathic pulmonary fibrosis. In an open-label, single-dose crossover study, the pharmacokinetics (PK) of pirfenidone were investigated with or without food and antacids in healthy adult volunteers. Concentrations of pirfenidone and its metabolites in plasma and urine were determined by liquid chromatography with tandem mass spectrometry, and candidate pharmacokinetic models were fit to plasma data using weighted, non-linear regression. The effect of food and antacids on pirfenidone exposure was evaluated by determining ‘equivalence’ using FDA guidelines. Adverse events were recorded by site personnel and classified by investigators on the basis of severity and relationship to study drug.Sixteen subjects yielded 64 pharmacokinetic profiles. The best fit was achieved using a five-compartment, linear model with an allowance for direct conversion to the primary metabolite (5-carboxy-pirfenidone). Coadministration with food decreased the rate and, to a lesser degree, the extent of pirfenidone absorption of absorption. Analysis of adverse events revealed a correlation between pirfenidone C_max and the risk of gastrointestinal (GI) adverse events, suggesting that food may reduce the risk of certain adverse events associated with pirfenidone. Administration of pirfenidone with food has a modest effect on overall exposure but results in lower peak concentrations, which may improve tolerability.     

Sodium and potassium content of liquid antacids.

Sodium and potassium contents of 37 commercially available liquid antacid preparations were estimated. Only nine preparations had sodium content below 60 mmol/L. The potassium content was below 1 mmol/L in 26 preparations. We conclude that caution should be exercised in selecting liquid antacid preparations in whom critically ill patients for electrolyte overload could prove harmful.     

Effects of fasting, refeeding, and fasting with T3 administration on Na-K,ATPase in rat skeletal muscle.

It is known that Na-K,adenosine triphosphatase (ATPase) in cell membranes represents an important consumer of cellular energy, eg, adenosine triphosphate (ATP), and that the concentration and activity of this enzyme change in a dose-dependent manner with serum thyroid hormone levels. To examine the hypothesis that low triiodothyronine (T3) syndrome represents a cellular adaptation in generalized severe illnesses that saves tissue energy expenditure, we measured the muscle Na-K,ATPase concentration and its activity in rats that led to low T3 syndrome induced by fasting. The Na-K,ATPase concentration was measured by 3H-ouabain binding to soleus muscle, and its activity was measured by 42K uptake in the contralateral soleus muscle. The effects of refeeding or T3 administration on Na-K,ATPase in soleus muscle in fasted rats were also examined. Na-K,ATPase concentration and activity were both increased in hyperthyroid rats and decreased in hypothyroid rats. In the fasting state, they were decreased to as low as the levels seen in hypothyroidism. Furthermore, with fasting + refeeding or fasting + T3 administration, Na-K,ATPase in soleus muscle returned to the normal level. These results suggest that tissue energy expenditure, as assessed by Na-K,ATPase, in skeletal muscles of fasted rats with low T3 syndrome is actually decreased to levels seen in hypothyroidism, due at least partly to the decrease in serum T3 concentrations, and that there exist some adaptation mechanisms in the peripheral tissues for the accommodation of energy metabolism in the body through decreased thyroxine (T4) to T3 conversion.     

In vitro tests overestimatein vivo neutralizing capacity of antacids in presence of food

The neutralizing capacity of two antacids (Alucol®=A, Syntrogel®=S), differing both in their composition and theoretical neutralizing capacity, was evaluatedin vitro andin vivo.In vitro at pH 3.5, 1 ml of A or S neutralizes 3.9 and 1.6 meq of acid, respectively, in an aqueous solution. When testedin vivo in the absence of food during near maximal acid secretion, induced by impromidine, 60 ml of either A or S reduced the 4-hr mean H⁺ activity by 83% and 65%, respectively. In contrast, the reduction of the 12-hr H⁺ activity observed after repeated administration of 30–60 ml of A or S at the end of the postprandial hour failed to reach significance with both preparations. This suggests that interaction with food produces a considerable loss ofin vivo antacid neutralizing capacity, not quantitatively predictable fromin vitro tests.     

Effect of long-term treatment with cimetidine and antacids in Barrett's oesophagus.

The effect of a long-term treatment (one to two years) with cimetidine (1.6 g per day) and an antacid (Regla pH) was evaluated in nine patients with a Barrett's oesophagus. The results showed that such long-term treatment had a beneficial effect on the symptoms and endoscopic signs of oesophagitis and on the healing of a Barrett's ulcer, but did not result in a regression of the squamocolumnar junction back towards the cardia. No significant changes were observed in the histological epithelial types in the biopsies taken below the squamocolumnar junction. No clinical or biochemical side-effects or changes in biochemical parameters were noted during this study.     

Triiodothyronine-receptor complex in rat brain: effects of thyroidectomy, fasting, food restriction, and diabetes

In vitro saturation analysis combined with quantification of T3, by an isotopic equilibrium technique or RIA, were used to examine the effects of thyroidectomy, fasting, diabetes, and food restriction on T3 concentration and specific binding in cerebral cortex and cerebellum. Fasting and food restriction did not affect the T3 binding parameters in the brain areas studied. Both thyroidectomy and diabetes were accompanied by a reduction in T3 content in nuclei from both cerebral cortex and cerebellum, but a decrease in T3 binding sites was only observed in both brain areas of diabetic animals. No significant differences in the binding affinity values among the experimental groups were seen. The diabetes-induced decrease in T3 content and receptor number were completely reversed by insulin treatment. Studies with fractionated nuclei from cerebral cortex and cerebellum showed that diabetes resulted in a reduction in T3 content and the number of receptors in glial nuclei from both brain areas. Although T3 content was also decreased in neuronal nuclei, the receptor concentration in these nuclear preparations did not change in concentration or affinity under the same conditions. These observations indicate that glial cells, not only have T3-binding characteristics similar to those of neuronal cells, but the T3 receptor number is decreased in the diabetes state.     

Gastric emptying of two radiolabelled antacids.

The rate of gastric emptying of two antacids, magaldrate and Maalox, was investigated using scintigraphy. Successful labelling of the antacids was carried out with 99mTc. The stability of the 99mTc-labelled antacids was satisfactory and there was no difference in antacid capacity between the labelled and unlabelled antacids. The studies were carried out on 15 healthy male volunteers. After an eight hour fast each subject ingested a standardised meal of 95.7 MJ (400 kcal). One hour later 10 ml of one of the two antacids previously labelled with 99mTc was administered. Serial detection by anterior and posterior projection of the amount of antacid retained in the stomach was performed to determine gastric emptying of antacid. One week later the study was repeated under the same conditions with the other antacid also labelled with 99mTc. The mean (SD) percentages of antacid retained in the stomach fit a linear model with a t1/2 of 86.6 (15.3) minutes for magaldrate and 52.3 (5.2) minutes for Maalox (p less than 0.01). When the mean percentages of retention at six time intervals were compared for both antacids, it was found that Maalox emptied much faster (p less than 0.01 at 15 and 30 minutes, p less than 0.02 at 45, 60, 75, and 90 minutes).