The effect of different dosage schedules of cisapride on gastric emptying in idiopathic gastroparesis

Summary The aim of this study was to determine the optimal dosage regimen of cisapride for the treatment of idiopathic gastroparesis.We studied 17 patients with documented idiopathic gastroparesis in a three-way, cross-over, double-blind study with three 4-day treatment periods separated by at least 3 days without treatment. In each period, the patients were preloaded with cisapride (10 mg tid) for three days. On the fourth day (the test day) they took either 10 mg or 20 mg before breakfast and placebo before lunch (1×10 mg), (1×20 mg), or 10 mg before breakfast and 10 mg before lunch (2×10 mg). The medications were taken 30 min before meals. Gastric emptying of solids (^99mTc-sulphur colloid) was measured at lunch time under basal conditions and during each treatment period. Plasma concentrations of cisapride were determined before the breakfast dose, before the lunch dose, and at 1, 2, 3, 4 and 5 h after.The greatest acceleration in gastric emptying occurred with the 2×10 mg regimen. Although the single morning dose of 20 mg also significantly accelerated gastric emptying (P=0.05), the reduction was not as substantial.Plasma concentrations of cisapride were significantly higher after 2×10 mg than after 1×20 mg or 1×10 mg. There was a significant relation between cisapride plasma concentrations and changes in gastric emptying. Peak concentrations of cisapride greater than 60 ng·ml^–1 were invariably associated with acceleration of gastric emptying.We conclude that cisapride 10 mg tid before meals is the optimal dose for the treatment of idiopathic gastroparesis.     

Metformin efficacy and tolerance in obese non-insulin dependent diabetics: a comparison of two dosage schedules

A comparative open study of metformin unit doses of 500 mg and 850 mg was carried out in 64 obese, non-insulin dependent diabetics on 1.5 to 3 g metformin daily. Glycaemic response, blood lactate, plasma metformin concentrations and tolerance for metformin were assessed. On changing from a 500 mg unit dose to an equivalent total dose of metformin using the 850 mg preparation, there were no significant changes in the random blood glucose, glycated haemoglobin, or blood lactate concentrations. Metformin plasma concentrations remained unchanged except for patients transferred from 1.5 to 2.0 g daily to 850 mg twice daily; in these patients plasma concentrations increased from 1.83 +/- 0.87 to 2.50 +/- 0.89 micrograms/l (p less than 0.01). Seven patients (3 asymptomatic and 4 with background symptoms) became intolerant of the 850 mg regimen and required to return to the 500 mg dose regimen. After exclusion of patients intolerant of the 850 mg dose regimen (11%), the remaining patients noted no significant change in symptoms and 28% of all patients transferred to the 850 mg dose unit indicated an overall preference for this regimen.     

Metformin efficacy and tolerance in obese non-insulin dependent diabetics: a comparison of two dosage schedules

Summary

A comparative open study of metformin unit doses of 500?mg and 850?mg was carried out in 64 obese, non-insulin dependent diabetics on 1.5 to 3?g metformin daily. Glycaemic response, blood lactate, plasma metformin concentrations and tolerance for metformin were assessed. On changing from a 500?mg unit dose to an equivalent total dose of metformin using the 850?mg preparation, there were no significant changes in the random blood glucose, glycated haemoglobin, or blood lactate concentrations. Metformin plasma concentrations remained unchanged except for patients transferred from 1.5 to 2.0?g daily to 850?mg twice daily; in these patients plasma concentrations increased from 1.83±0.87 to 2.50±0.89 μg/l (p < 0.01). Seven patients (3 asymptomatic and 4 with background symptoms) became intolerant of the 850?mg regimen and required to return to the 500?mg dose regimen. After exclusion of patients intolerant of the 850?mg dose regimen (11%), the remaining patients noted no significant change in symptoms and 28% of all patients transferred to the 850?mg dose unit indicated an overall preference for this regimen.     

Aluminum hydroxide: evaluation of two dosage forms and two dosing schedules in reducing intestinal phosphate absorption

A crossover, randomized, eight-week trial using eight adult volunteers was undertaken to (1) determine the efficacy of aluminum hydroxide in decreasing gastrointestinal phosphate absorption, (2) compare the effectiveness of "with meal" and "between meal" dosing schedules, and (3) compare the effectiveness of the capsule and liquid dosage forms. Four treatments, each with a daily dose of approximately 6 g, were taken on a three-times-a-day regimen. The effectiveness of the treatment regimens was measured by using two variables: the decrease in total urinary phosphorus excretion, and the increase in the percent tubular reabsorption of phosphorus (TRP). Aluminum hydroxide treatment produced a significant change in urinary phosphorus excretion (p less than 0.0005) and in percent TRP (p less than 0.0005). For the study population, total urinary phosphorus excretion was the determining factor in changing the percent TRP. The increase in TRP and the decrease in total urinary phosphorus excretion was of the same degree regardless of dosage form or dosage schedule. Aluminum hydroxide was effective in decreasing phosphorus absorption as measured in this study. It appears that aluminum hydroxide capsules could be used with equal efficacy as the liquid dosage form in controlling hyperphosphatemia in patients with chronic renal failure who will not comply with a treatment program using the liquid.     

角膜塑型术矫治近视200例

目的:探讨角膜塑型术(Ortho-K镜)对近视矫正的作用及控制近视发展的长期效果.方法:对200例配戴Ortho-K镜满6年的青少年近视患者的临床资料进行分析,以了解其相关指标的变化情况.200例386只眼配戴前裸眼视力0.31±0.21,屈光度-3.81±2.78 D,角膜曲率44.51±3.53,BUT时间18.28±8.14 s,眼压值2.13±0.67 kPa,内皮细胞计数2 859±851,角膜中央厚度544±68 μm.结果:随访6年未见严重并发症发生,患者视力得到显著提升(P＜0.05),屈光度和角膜曲率比较有显著性降低(P＜0.01),角膜内皮细胞计数和角膜中央厚度未见明显改变(P＞0.05).结论:角膜塑型术作为一种非创伤性矫正近视的手段,能有效降低近视屈光度,控制近视发展.     

Effects of drugs on responding under concurrent fixed-interval schedules and concurrent fixed-ratio schedules

Pigeons were trained to respond under concurrent fixed-interval fixed-interval (concurrent FI FI) schedules with Fl values (in seconds) of 30/300, 60/240, 60/60, 240/60 and 300/30. A second group was trained to respond under concurrent fixed-ratio fixed-ratio (concurrent FR FR) with FR values of 10/40, 10/20, 20/20, 20/10 and 40/10. Under the concurrent Fl Fl schedules, pigeons responded much less often on the key with the higher reinforcement density than would be predicted basing on a perfect matching of the ratio of responses made to the ratio of reinforcers delivered, and the pigeons also showed a bias towards responding on the left key. Pentobarbital, methamphetamine, morphine and phencyclidine had little effect on bias, but high doses of methamphetamine, morphine and phencyclidine decreased undermatching. Under the concurrent FR FR schedules, pigeons responded almost entirely on the key with the higher reinforcement density. Only pentobarbital consistently disrupted this pattern of responding.     

Gastroretentive dosage forms

Gastroretentive dosage forms are drug delivery systems which remain in the stomach for an extended period of time, and allow both spacial and time control of drug liberation. Their application can be advantageous in the case of drugs that are absorbed mainly from the upper part of the gastrointestinal tract or are unstable in the medium of distal intestinal regions. They can also be used beneficially in the local therapy of the stomach. Because of the complicated and by many factors influenced physiology of this organ, the design of such delivery systems is a task requiring due foresight and knowledge. Gastroretentive dosage forms can be floating, expandable, bioadhesive, modified shape and high density systems according to the physical property leading to prolongation of gastric residence time. Combinations of the listed categories can occur as well. Several spirited ideas and solutions have come up in the literature for the preparation of such delivery systems, but there is still need for development in the field of implementation and prediction of in vivo behaviour before these dosage forms can be elemental part of clinical practice.     

Alternative work schedules for female pharmacists

The impact of the increased proportion of women in pharmacy is discussed, and two leadership positions for which part-time work schedules were implemented are described. Issues associated with the increased representation of women include pharmacist shortages, loss of future leaders, decreased staff productivity related to inadequate day-care services, and a reduced earning potential of pharmacists. Many of these problems can be addressed by altering benefit packages and work schedules to enable employees to raise children while continuing to work. Specific strategies include legislation, day-care programs, flex time and flex scheduling, telecommuting, and the creation of alternative work schedules or permanent part-time positions. At the University of Michigan, a part-time position that combines faculty and clinical responsibilities has been in place since 1988. At The Washington Hospital Center, one of the three assistant director of pharmacy positions is part-time. The women in both positions have met or exceeded job performance requirements while raising a family. Issues raised by the increasing number of female pharmacists must be addressed by the profession. Part-time work schedules are one strategy for enabling female pharmacists to meet both their family and career responsibilities.     

Shaping smoking cessation using percentile schedules

Behavioral interventions that provide incentives contingent upon abstinence are effective addiction treatments. Nevertheless, these treatments often fail for individuals whose recent behaviors are very different from those reinforced. These hard-to-treat individuals may require shaping to achieve abstinence. We used percentile schedules to shape smokers' delivery of breath samples indicative of recent smoking abstinence (breath carbon monoxide (BCO) <4 ppm). Percentile schedules deliver incentives to current behaviors proximal to the target. Participants (N = 102) were assigned to treatments delivering incentives for breath COs at or below the 10th, 30th, 50th, or 70th percentile of recent breath COs. Each condition effectively ensured contact with available contingencies, and resulted in BCO <4 ppm in >90% of the 30th, 50th and 70th percentile groups versus 63% in the 10th percentile. The 30th, 50th and 70th percentiles were especially effective in a sub-sample of hard-to-treat participants who did not deliver a breath CO <4 ppm during an initial abstinence test or during a nine-visit baseline period, suggesting the value of shaping for this important sub-sample.     

Individualized adjustment of vancomycin dosage: comparison with two dosage nomograms

An individualized method of vancomycin dosage adjustment using steady-state serum concentrations was assessed in 50 patients (86 sets of vancomycin serum concentrations). The predictive accuracy of this method was compared with that of two published nomograms (Moellering, Matzke). Peak and trough serum concentrations predicted from previously drawn vancomycin serum concentrations (individualized method) using a one-compartment pharmacokinetic model were compared with measured steady-state peak and trough serum concentrations. Predicted peak and trough serum concentrations were also generated for both the Moellering and Matzke nomograms by using the elimination rate constant derived from each of the respective nomograms and the fixed volume of distribution (0.9 L/kg) assumed by the nomograms, and the actual administered vancomycin dose and dosage interval. These predicted concentrations were also compared with the measured peak and trough concentrations. Statistical measures of bias and precision indicated that the individualized method of dosage adjustment more closely predicted vancomycin serum concentrations following a dosage change than did either of the nomograms. Overall, the Moellering nomogram was the least accurate of the three methods in predicting vancomycin serum concentrations, and this nomogram should not be used to titrate vancomycin dosages in a clinical setting. Adjustment of vancomycin dosages should be individualized based on pharmacokinetic data derived from measured serum concentrations. In situations where quantitative analysis of vancomycin concentrations is not available, the Matzke nomogram appears to be a reasonable method of adjusting vancomycin dosages.