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Clinical Data Management and Statistical Design in the Clinical Research Process
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
Joseph R. Assenzo, Thomas W. Teal
The crossover design has a great deal of intuitive appeal and is used extensively in clinical pharmacology studies. In the two-treatment crossover, patients are allocated randomly to two groups. The first group receives treatments in the order AB and the second group in the order BA. This approach permits comparison of both treatments in the same patients. The advantage of a crossover is related to the relative magnitude of within-patient variation to between-patient variation. Brown [21] in a comprehensive evaluation of the design, has constructed a table which gives cost efficiency of the crossover relative to the completely randomized experiment for various ratios of between to within-patient variation. Any efficiencies which can be obtained with the crossover must be balanced with the major criticism of the design: carryover effects cannot be detected in a satisfactory manner. Brown concludes that "the crossover experiment can yield great savings in cost if the assumption of no carryover effect is valid, but the design should not be used if this assumption is in doubt."
Microbiological Assay of Antibiotics in Body Fluids and Tissues
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Although preliminary estimates of new antibiotic kinetics can be ascertained in laboratory animals, and sometimes the agreement is good [2], these estimates must be verified in humans. Such experiments begin by dosing normal, healthy, usually young adult males, and taking blood and urine samples at high frequency–often 15 or 16 blood samples in 24 hr and urine at 2 hr intervals. A simple twoway crossover experiment with 15 subjects can thus generate 450 samples for analysis, and several of these experiments can be run each week in the clinic by a small staff of physicians and nurses provided with an adequate pool of volunteers. Once doses, routes of administration, and kinetics of elimination are eatablished, dosage formulations, interaction with other antibiotics, and trials in the elderly, children, women, and volunteers with various diseases are begun. Sample types are expanded to include all the readily available body fluids in addition to blood and urine, such as milk, cerebrospinal, visceral, and synovial fluids, feces, and bile. Volunteer patients undergoing surgery are dosed, and each type of tissue encountered in the surgery, is sampled for assay of its antibiotic content. An example of the tissue samples taken for assay of aztreonam is shown in Table 1. All these samples are characterized by relatively low concentrations of the antibiotic in a complex matrix and, usually, sample sizes in the range of only 100–200 mg.
The Importance of Personalized Nutrition in Psychological Disorders
Published in Nilanjana Maulik, Personalized Nutrition as Medical Therapy for High-Risk Diseases, 2020
There is also a relationship between selenium supplementation and postpartum depression (Mokhber, Namjoo et al. 2011). Another double-blind crossover experiment, conducted in Britain on 50 people, demonstrated that selenium intake of 100 g/day for five weeks reduces the symptoms of depression, and the effect was more significant in those with lower selenium intake levels (Benton and Cook 1991). On the other hand, an experiment with a larger randomized-controlled trial among 501 elderly volunteers in the UK showed no such effect (Rayman, Thompson et al. 2006).
Safety issues of psilocybin and LSD as potential rapid acting antidepressants and potential challenges
Published in Expert Opinion on Drug Safety, 2022
Giordano Novak Rossi, Jaime E. C. Hallak, José Carlos Bouso Saiz, Rafael G. Dos Santos
The next study analyzed was published in 2016 by Griffiths and collaborators [18]. This was a preliminary, double-blind, randomized, placebo-controlled crossover experiment with 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. Psilocybin was administered in an active treatment dose of 22 or 30 mg with results being compared with an active placebo of psilocybin with doses of 1 or 3 mg. The experimental treatment group showed augmented HR (prevalence not reported), SBP (34%), and DBP (12%) when compared with the active placebo group (all p’s < 0.05). Other AEs were assessed with researcher’s evaluations, participant’s reports and items from MRQ and 5D-ASC. The most prevalent during the experimental treatment sessions included psychological discomfort (32%), anxiety (26%), physical discomfort (21%), and nausea or vomiting (15%). Notably, one participant presented a transient episode of paranoid ideation (2%). All items from the 5D-ASC were significantly altered by the high dose when compared with the low dose, including dread of ego dissolution and auditory alterations (both highly augmented, p’s < 0.001). The next day after treatment, 2 of 11 participants (in whom headaches were assessed) reported having a headache. Nevertheless, there were no reports of serious AEs with most resolving by the end of the experimental sessions (as reported by the authors). None of the participants required medical intervention and there were no cases of HPPD or prolonged psychosis.
Fructose and hepatic insulin resistance
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
Samir Softic, Kimber L. Stanhope, Jeremie Boucher, Senad Divanovic, Miguel A. Lanaspa, Richard J. Johnson, C. Ronald Kahn
Studies of acute and chronic fructose supplementation on ad libitum diets still leave the question of whether or not isocaloric fructose intake has an effect on hepatic insulin resistance. This question was addressed in a crossover experiment in which eight healthy men consumed weight-maintaining, isocaloric diets containing either high-fructose (25% energy requirement) or low-fructose diet (starch provided in place of fructose) for nine days. In this study, subjects exhibited lower suppression of hepatic glucose production during a euglycemic-hyperinsulinemic clamp when they consumed the high-fructose diet, compared to the low-fructose diet [19]. Hallfrisch et al. [20] also conducted a crossover study in which twelve men with hyperinsulinemia and twelve healthy age- and BMI-matched men were provided standardized equicaloric meals that contained either 0, 7.5, or 15% of the energy requirement as fructose in solid food for five weeks. All other components of the diet were matched so that the participants received 43% of the calories as total carbohydrate, 42% as fat and 15% as protein. Compared with the 0% fructose diet, the 15% fructose diet increased glucose and insulin responses to a 3-h oral sucrose tolerance test [20]. As above, the studies that utilized euglycemic-hyperinsulinemic clamps to index both whole body and hepatic insulin resistance suggest that development of hepatic insulin resistance precedes development of whole body insulin resistance [18,19].
The therapeutic potential of CETP inhibitors: a patent review
Published in Expert Opinion on Therapeutic Patents, 2018
Xinran Wang, Wei Li, Lijuan Hao, Honglei Xie, Chenzhou Hao, Chunchi Liu, Wenyan Li, Xuqiong Xiong, Dongmei Zhao
WO2014076568 relates to a series of pharmaceutical compositions of CETP inhibitors and the active ingredients are the compounds of formula 8 (Figure 2) [33]. This invention provided a method to prepare the compound; meanwhile, it patented the preparation of the pharmaceutical compositions. Compound 8c was selected to make capsules and tablets, and then a pharmacokinetic study was conducted in male Beagle dogs under fed and fasted conditions [34–36]. In this randomized crossover experiment, the compositions were administered at a dose level of 200 mg/kg, and compound 8c exhibited an acceptable pharmacokinetic profile with the Cmax = 1.71 ± 0.41 μM and AUC = 21.1 ± 3.73 μM h under the fed state, while Cmax = 0.94 ± 0.77 μM and AUC = 9.81 ± 7.38 μM h were achieved in the fasted state. Next, the compositions that contain compound 8c and various pharmaceutical adjuvants were subjected to a dissolution procedure in simplified simulated intestinal fluid. The amount of drug released revealed a better dissolution curve of patented compositions, as half of the drugs were released in 1 h.