scholarly journals The 1β-Hydroxy-Deoxycholic Acid to Deoxycholic Acid Urinary Metabolic Ratio: Toward a Phenotyping of CYP3A Using an Endogenous Marker?

2021 ◽  
Vol 11 (2) ◽  
pp. 150
Author(s):  
Gaëlle Magliocco ◽  
Jules Desmeules ◽  
Marija Bosilkovska ◽  
Aurélien Thomas ◽  
Youssef Daali
Keyword(s):  
Clinical Trial ◽  
Healthy Volunteers ◽  
Short Duration ◽  
Deoxycholic Acid ◽  
Metabolic Ratio ◽  
Control Session ◽  
Induction Ratio ◽  
Pre Treatment ◽  
Larger Sample ◽  
Potential Use

In this study, we assessed the potential use of the 1β-hydroxy-deoxycholic acid (1β-OH-DCA) to deoxycholic acid (DCA) urinary metabolic ratio (UMR) as a CYP3A metric in ten male healthy volunteers. Midazolam (MDZ) 1 mg was administered orally at three sessions: alone (control session), after pre-treatment with fluvoxamine 50 mg (12 h and 2 h prior to MDZ administration), and voriconazole 400 mg (2 h before MDZ administration) (inhibition session), and after a 7-day pre-treatment with the inducer rifampicin 600 mg (induction session). The 1β-OH-DCA/DCA UMR was measured at each session, and correlations with MDZ metrics were established. At baseline, the 1β-OH-DCA/DCA UMR correlated significantly with oral MDZ clearance (r = 0.652, p = 0.041) and Cmax (r = −0.652, p = 0.041). In addition, the modulation of CYP3A was reflected in the 1β-OH-DCA/DCA UMR after the intake of rifampicin (induction ratio = 11.4, p < 0.01). During the inhibition session, a non-significant 22% decrease in 1β-OH-DCA/DCA was observed (p = 0.275). This result could be explained by the short duration of CYP3A inhibitors intake fixed in our clinical trial. Additional studies, particularly involving CYP3A inhibition for a longer period and larger sample sizes, are needed to confirm the 1β-OH-DCA/DCA metric as a suitable CYP3A biomarker.

Planning the Size of Clinical Trials with Allowance for Patient Noncompliance

1990 ◽  
Vol 29 (03) ◽  
pp. 243-246 ◽  
Author(s):  
M. A. A. Moussa
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sample Size ◽  
Event Rate ◽  
Survival Functions ◽  
Time Intervals ◽  
Patient Noncompliance ◽  
Event Rates ◽  
Larger Sample

AbstractVarious approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns.

The influence of taurine and L-carnitine on 6 β-hydroxycortisol/cortisol ratio in human urine of healthy volunteers

2019 ◽  
Vol 34 (3) ◽  
Author(s):  
Anna A. Makhova ◽  
Eugenia V. Shikh ◽  
Tatiana V. Bulko ◽  
Zhanna M. Sizova ◽  
Victoria V. Shumyantseva
Keyword(s):  
Catalytic Activity ◽  
Healthy Volunteers ◽  
Human Urine ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Metabolic Ratio ◽  
Urine Samples ◽  
Cyp3a4 Activity ◽  
Active Compounds ◽  
Cortisol Ratio

Abstract Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6β-hydroxycortisol/cortisol (6β-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6β-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6β-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6β-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6β-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6β-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6β-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6β-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.

scholarly journals Residual gastric volume evaluation with ultrasonography after ingestion of carbohydrate- or carbohydrate plus glutamine-enriched beverages: a randomized, crossover clinical trial with healthy volunteers

2017 ◽  
Vol 54 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Paulo Cesar GOMES ◽  
Cervantes CAPOROSSI ◽  
Jose Eduardo AGUILAR-NASCIMENTO ◽  
Ageo Mario Candido da SILVA ◽  
Viviane Maeve Tavares de ARAUJO
Keyword(s):  
Clinical Trial ◽  
Healthy Volunteers ◽  
Postoperative Recovery ◽  
Gastric Volume ◽  
Safe Procedure ◽  
Abdominal Ultrasonography ◽  
Residual Gastric Volume ◽  
Potential Benefits ◽  
The Mean ◽  
To Receive

ABSTRACT BACKGROUND Abbreviation of preoperative fasting to 2 hours with maltodextrin (CHO)-enriched beverage is a safe procedure and may enhance postoperative recovery. Addition of glutamine (GLN) to CHO beverages may include potential benefits to the metabolism. However, by adding a nitrogenous source to CHO beverages, gastric emptying may be delayed and increase the risk of bronchoaspiration during anesthesia. OBJECTIVE In this study of safety, we aimed at investigating the residual gastric volume (RGV) 2 hours after the intake of either CHO beverage alone or CHO beverage combined with GLN. METHODS We performed a randomized, crossover clinical trial. We assessed RGV by means of abdominal ultrasonography (US) in 20 healthy volunteers (10 males and 10 females) after an overnight fast of 8 hours. Then, they were randomized to receive 600 mL (400 mL immediately after US followed by another 200 mL 2 hours afterwards) of either CHO (12.5% maltodextrin) or CHO-GLN (12.5% maltodextrin plus 15 g GLN). Two sequential US evaluations were done at 120 and 180 minutes after ingestion of the second dose. The interval of time between ingestion of the two types of beverages was 2 weeks. RESULTS The mean (SD) RGV observed after 8 hours fasting (13.56±13.25 mL) did not statistically differ (P>0.05) from the RGV observed after ingesting CHO beverage at both 120 (16.32±11.78 mL) and 180 minutes (14.60±10.39 mL). The RGV obtained at 120 (15.63±18.83 mL) and 180 (13.65±10.27 mL) minutes after CHO-GLN beverage also was not significantly different from the fasting condition. CONCLUSION The RGV at 120 and 180 minutes after ingestion of CHO beverage combined with GLN is similar to that observed after an overnight fast.

Screening and Recruitment Procedures of Healthy Volunteers In A Phase I Clinical Trial Unit: Experience In 64 Bioequivalence Studies

2015 ◽  
Vol 37 (8) ◽  
pp. e129
Author(s):  
B. Duque ◽  
A.M. Borobia ◽  
R. Lubomirov ◽  
E. Ramirez ◽  
P. Guerra ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Healthy Volunteers ◽  
Clinical Trial Unit ◽  
Phase I Clinical Trial

scholarly journals A clinical trial on the acute effects of methadone and buprenorphine on actual driving and cognitive function of healthy volunteers

2018 ◽  
Vol 85 (2) ◽  
pp. 442-453 ◽  
Author(s):  
Maren Cecilie Strand ◽  
Vigdis Vindenes ◽  
Hallvard Gjerde ◽  
Jørg Gustav Mørland ◽  
Johannes G. Ramaekers
Keyword(s):  
Clinical Trial ◽  
Cognitive Function ◽  
Healthy Volunteers ◽  
Acute Effects

scholarly journals Effect of Red Wine Intake on Serum and Salivary Melatonin Levels: A Randomized, Placebo-Controlled Clinical Trial

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2474 ◽  
Author(s):  
Elena Varoni ◽  
Rita Paroni ◽  
Jacopo Antognetti ◽  
Giovanni Lodi ◽  
Andrea Sardella ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Healthy Volunteers ◽  
Red Wine ◽  
Statistical Significance ◽  
Serum Levels ◽  
Controlled Clinical Trial ◽  
Salivary Melatonin ◽  
The One ◽  
To Receive

Melatonin (MLT) is a recently discovered phytochemical in wine, but its influence on physiological MLT levels is still unknown. This study aimed at evaluating variations, in serum and saliva, of MLT concentrations after the intake of MLT-enriched red wine. Twelve healthy volunteers were recruited to receive 125 mL of red wine naturally lacking of MLT (placebo, PLC), or the same wine enriched with MLT (MLT+). A physiological steady decline of serum MLT was observed from baseline up to 90 min, for both wines. After PLC intake, the decrease was significantly faster than the one occurring after MLT+ wine, which thus delayed the drop down of serum MLT with a plateau at 30–60 min. Salivary MLT levels slightly peaked at 45 min after MLT+ wine intake, without statistical significance. Therefore, the intake of a glass of MLT-enriched red wine changed serum levels of the indoleamine, supporting the role of wine MLT in counteracting the physiological decline of the hormone into the bloodstream.

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