scholarly journals Grepafloxacin in Patients with Acute Bacterial Exacerbations of Chronic Bronchitis - a Question of Speed in Bacterial Killing

1998 ◽  
Vol 9 (suppl e) ◽  
pp. 16E-22E
Author(s):  
Jerome J Schentag
Keyword(s):  
Chronic Bronchitis ◽  
Clinical Cure ◽  
Area Under The Curve ◽  
Response Probability ◽  
Systemic Absorption ◽  
Double Blind ◽  
Bacterial Killing ◽  
Pharmacodynamic Analysis ◽  
X 24 ◽  
Dose Response Study

OBJECTIVE: To characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis (ABECB), with particular attention to the speed of bacterial killing. This was possible because the study design incorporated daily cultures of the patients’ sputum.PATIENTS AND METHODS: The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age who were part of a multicentre, randomized, double-blind, dose-response study. Patients were randomly assigned to receive oral regimens of grepafloxacin - 200, 400 or 600 mg - each administered once daily for 14 days. Daily cultures and quantitative Gram stains from serial 24 h collections of sputum were used to determine the days to eradication of each strain of bacteria. Grepafloxacin plasma concentration profiles were best fit by a pharmacokinetic model with first order absorption following a lag time between administration of the dose and onset of systemic absorption. Pharmacodynamic analysis was performed for three measures of antibacterial response: probability of bacteriological cure and probability of clinical cure, and time to eradication.RESULTS: All three measures of response were strongly related to the 24 h area under the inhibitory curve (AUIC) (area under the curve/minimum inhibitory concentration). At an AUIC below of 75/serum inhibiting titre (SIT) x 24 h, the percentage probability of clinical cure was 71 %; at an AUIC between 75 and 175, it was 80% (P<0.05); and, at an AUTC above 175, it was 98% (P<0.01).CONCLUSION: The speed of bacterial killing for grepafloxacin in ABECB patients was highly related to AUIC; values below 75 appear inadequate, and values greater than 175 were optimal.

scholarly journals Dietary Supplementation with Casein Glycomacropeptide, Leucine and Tryptophan Reduces Plasma Amino Acid Levels in Men

2021 ◽  
pp. 1-28
Author(s):  
Erik Roj Larsen ◽  
Anette Juel ◽  
Erik Jensen ◽  
Tristan R. Hollyer ◽  
Gregers Wegener
Keyword(s):  
Amino Acids ◽  
Area Under The Curve ◽  
Aromatic Amino Acids ◽  
Bipolar Disorders ◽  
Double Blind ◽  
Amino Acid Levels ◽  
The One ◽  
Dose Response Study ◽  
Dose Dependent ◽  
Different Doses

Abstract Background The treatment of mania in bipolar disorders needs to be more efficient, as the manic condition creates severe problems for the patient when it comes to work, finances, relationships, and health. This proof-of-concept study examines to what extent casein glycomacropeptide (CGMP) may reduce the precursors of dopamine, phenylalanine, and tyrosine, in plasma, and therefore be a potential new intervention to treat acute manic episodes. Method The study was designed as a double-blind randomised dose-response study of CGMP (with added leucine and tryptophan) in 15 healthy men, receiving 3 different doses of CGMP with an interval of at least 14 days. Results Administration of CGMP produced a dose dependent depletion of plasma aromatic amino acids. The total area under the curve of plasma ratios of phenylalanine-tyrosine compared to the level of leucine-isoleucine-valine-tryptophan was CGMP(20g): 3.648 [SE:0.3281]; CGMP(40g): 2.368 [SE:0.1858]; CGMP(60g)1.887 [SE:0.2591]. A comparison of the groups showed a dose dependent statistical difference, with a One-Way ANOVA summary (Dunnett) F= 11.87, p= 0.0003, CGMP 20g vs CGMP 40g, p= 0.0042, CGMP 20g vs CGMP 60g, p= 0.0002. No significant side effects were observed. Conclusions This study demonstrate CGMP is a well-tolerated and effective mixture, and that 60 g CGMP produced the highest depletion of plasma aromatic amino acids (phenylalanine and tyrosine). The effect seems to be highest after 3-4 hours. We therefore conclude that this dose should be the one considered for future studies involving CGMP in humans.

scholarly journals Single Ingestion of Trehalose Enhances Prolonged Exercise Performance by Effective Use of Glucose and Lipid in Healthy Men

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1439
Author(s):  
Naomi Hamada ◽  
Tsuyoshi Wadazumi ◽  
Yoko Hirata ◽  
Mayumi Kuriyama ◽  
Kanji Watanabe ◽  
...  
Keyword(s):  
Exercise Performance ◽  
Prolonged Exercise ◽  
Insulin Response ◽  
Area Under The Curve ◽  
Constant Load ◽  
Bicycle Ergometer ◽  
The Body ◽  
Water Control ◽  
Double Blind ◽  
Healthy Men

Trehalose increases blood glucose levels slowly and induces a slight insulin response. The present study aimed to study the effect of trehalose on prolonged exercise performance. The participants were 12 healthy men (age: 21.3 ± 0.9 y). After an overnight fast (12 h), they first exercised with a constant load (intensity: 40% V˙O2peak) for 60 min using a bicycle ergometer. They continued to exercise with a constant load (40% V˙O2peak) for 30 min between four sets of the 30-s Wingate test. After the 1st set, each participant ingested 500 mL water (control), 8% glucose, or 8% trehalose in three trials. These three trials were at least one week apart and were conducted in a double-blind and randomized crossover manner. Blood was collected for seven biochemical parameters at 12 time points during the experiment. The area under the curve of adrenaline after ingestion of trehalose was significantly lower than that for water and tended to be lower than that for glucose in the later stage of the exercise. Lower secretion of adrenaline after a single dose of 8% trehalose during prolonged exercise reflected the preservation of carbohydrates in the body in the later stage of the exercise. In conclusion, a single ingestion of trehalose helped to maintain prolonged exercise performance.

scholarly journals A Double-Blind, Dose-Response Study of the Efficacy and Safety of Olmesartan Medoxomil in Children and Adolescents with Hypertension

Hypertension ◽  
2010 ◽  
Vol 55 (6) ◽  
pp. 1323-1330 ◽  
Author(s):  
Lydie Hazan ◽  
Oscar A. Hernández Rodriguez ◽  
As'ad E. Bhorat ◽  
Koichi Miyazaki ◽  
Ben Tao ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Dose Response ◽  
Olmesartan Medoxomil ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Dose Response Study

Patient self-reporting of tolerability using PRO-CTCAE: A randomized double-blind placebo controlled phase II trial comparing gemcitabine in combination with adavosertib or placebo in women with platinum resistant epithelial ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5541-5541
Author(s):  
Ainhoa Madariaga ◽  
Sandra A. Mitchell ◽  
Tyler Pittman ◽  
Lisa Wang ◽  
Valerie Bowering ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Abdominal Pain ◽  
Objective Assessment ◽  
Area Under The Curve ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Self Report ◽  
Double Blind ◽  
Patient Reported ◽  
Fatigue Severity

5541 Background: A 4 month improvement in OS was demonstrated when Wee1 inhibitor adavosertib (Ad) and gemcitabine (G; arm A) was compared to G and placebo (P; arm B) in a phase 2 trial in recurrent ovarian cancer (NCT02151292). The patient reported outcome version of the CTCAE (PRO-CTCAE) was used to capture self-report of the frequency, severity and/or interference (scored 0-4; higher scores indicating worse symptomatic adverse events [syAEs]). Methods: Ad/P was given orally on D1-2, D8-9, D15-16 with G D1, D8, D15 in a 28-day cycle. English speaking pts in 2 centres completed PRO-CTCAE items electronically in clinic at baseline, D1 and D15 of each cycle and off treatment. An exploratory objective was to characterize syAEs in the first 3 months of therapy. We calculated 12-week area under the curve (AUC12w) as a measure of syAE over time and incremental AUC12w (iAUC12w) for adjustment to baseline syAEs and compared arms A and B using an independent samples t-test. We assessed proportion of scores 3-4 at 6 time-points and compared them using Fisher’s Exact Test at each survey. Results: 51 pts were enrolled and completed ≥1 survey, 47 were evaluable for primary outcome (arm A: 28, B: 19). ECOG status was ≤1 in 44/47 pts. Median number of cycles of therapy were 5 (1-16) in arm A, and 2 (1-16) in B. Survey completion rates were high (arm A 93%, B 95%). Mean AUC12w fatigue severity (A 152 [standard error 9] vs B 112 [10]; p = 0.005) and interference (A 144 [11] vs 98 [15]; p = 0.018), diarrhea frequency (A 70 [12] vs B 33 [9]; p = 0.014), mucositis (A 23 [6] vs B 6 [3]; p = 0.012) and difficulty swallowing severity (A 10 [3] vs B 2 [2]; p = 0.023) were higher in arm A (any grade). There were no statistically significant between-arm differences in abdominal pain, bloating, nausea, vomiting and anxiety. The iAUC12w was significantly higher in arm A vs B for difficulty swallowing severity (A 10.1 [3] vs B -2.7 [4.7]; p = 0.02), mucositis severity (A 19.9 [6.6] vs B -3.1 [6.9]; p = 0.02) and fatigue severity (A 35.2 [8.2] vs B -3.1 [9.8]; p = 0.005). Proportions with high scores (3-4) were only significantly higher at C1D15 for fatigue severity in arm A (A 55% vs B 19%, p = 0.044). No significant differences were seen in other 3-4 scores per survey time. Conclusions: This is the first study evaluating pts self-reported toxicity with adavosertib in a randomized setting, allowing pts self-evaluation of toxicity in the context of improved PFS and OS. Greater fatigue, diarrhea, mucositis and difficulty swallowing were experienced by pts receiving adavosertib and gemcitabine, but score 3-4 reached significance on C1D15 fatigue only. No significant differences were detected in syAE profile for nausea, vomiting, abdominal pain, bloating and anxiety. This approach allows objective assessment of pts perception of toxicity with complex therapy. Clinical trial information: NCT02151292.

scholarly journals The Effect of an Encapsulated Nutrient Mixture on Food Intake and Satiety: A Double-Blind Randomized Cross-Over Proof of Concept Study

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1787 ◽  
Author(s):  
Annick Alleleyn ◽  
Mark van Avesaat ◽  
Dina Ripken ◽  
Sinéad Bleiel ◽  
Daniel Keszthelyi ◽  
...  
Keyword(s):  
Small Intestine ◽  
Food Intake ◽  
Area Under The Curve ◽  
Double Blind ◽  
Distal Small Intestine ◽  
Active Product ◽  
Non Invasive ◽  
Control Product ◽  
Scale Scores ◽  
And Control

Activation of the intestinal brake by infusing nutrients into the distal small intestine with catheters inhibits food intake and enhances satiety. Encapsulation of macronutrients, which protects against digestion in the proximal gastrointestinal tract, can be a non-invasive alternative to activate this brake. In this study, we investigate the effect of oral ingestion of an encapsulated casein and sucrose mixture (active) targeting the distal small intestine versus a control product designed to be released in the stomach on food intake, satiety, and plasma glucose concentrations. Fifty-nine volunteers received the active and control product on two separate test days. Food intake was determined during an ad libitum meal 90 min after ingestion of the test product. Visual analogue scale scores for satiety and blood samples for glucose analysis were collected at regular intervals. Ingestion of the active product decreased food intake compared to the control product (655 kcal compared with 699 kcal, respectively, p < 0.05). The area under the curve (AUC) for hunger was decreased (p < 0.05) and AUC for satiety was increased (p < 0.01) after ingestion of the active product compared to the control product. Ingestion of an encapsulated protein-carbohydrate mixture resulted in inhibition of food intake compared to a non-encapsulated control product.

Amino Acid Mixture Enriched With Arginine, Alanine, and Phenylalanine Stimulates Fat Metabolism During Exercise

2016 ◽  
Vol 26 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Keisuke Ueda ◽  
Yutaka Nakamura ◽  
Makoto Yamaguchi ◽  
Takeshi Mori ◽  
Masayuki Uchida ◽  
...  
Keyword(s):  
Fat Metabolism ◽  
Maximal Oxygen Consumption ◽  
Area Under The Curve ◽  
Oral Intake ◽  
Glucagon Secretion ◽  
Free Fatty Acid Level ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Double Blind ◽  
Maximum Serum

Although there have been many investigations of the beneficial effects of both exercise and amino acids (AAs), little is known about their combined effects on the single-dose ingestion of AAs for lipid metabolism during exercise. We hypothesize that taking a specific combination of AAs implicated in glucagon secretion during exercise may increase fat metabolism. We recently developed a new mixture, d–AA mixture (D-mix), that contains arginine, alanine, and phenylalanine to investigate fat oxidation. In a double-blind, placebo-controlled crossover study, 10 healthy male volunteers were randomized to ingest either D-mix (3 g/dose) or placebo. Subjects in each condition subsequently performed a physical task that included workload trials on a cycle ergometer at 50% of maximal oxygen consumption for 1 hr. After oral intake of D-mix, maximum serum concentrations of glycerol (9.32 ± 6.29 mg/L and 5.22 ± 2.22 mg/L, respectively; p = .028), free fatty acid level (0.77 ± 0.26 mEq/L and 0.63 ± 0.28 mEq/L, respectively; p = .022), and acetoacetic acid levels (37.9 ± 17.7 μmol/L and 30.3 ± 13.9 μmol/L, respectively; p = .040) were significantly higher than in the placebo groups. The area under the curve for glucagon during recovery was numerically higher than placebo (6.61 ± 1.33 μg/L • min and 6.06 ± 1.23 μg/L • min, respectively; p = .099). These results suggest that preexercise ingestion of D-mix may stimulate fat metabolism. Combined with exercise, the administration of AA mixtures could prove to be a useful nutritional strategy to maximize fat metabolism.

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