Effects of omeprazole and cimetidine on the urinary metabolic ratio of proguanil in healthy volunteers

1996 ◽  
Vol 50 (5) ◽  
pp. 417-419 ◽  
Author(s):  
A. A. Somogyi ◽  
H. A. Reinhard ◽  
F. Bochner
Keyword(s):  
Healthy Volunteers ◽  
Metabolic Ratio

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 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.

Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers

1999 ◽  
Vol 13 (6) ◽  
pp. 1230 ◽  
Author(s):  
B Schmekel ◽  
I Rydberg ◽  
B Norlander ◽  
K.n Sjöswärd ◽  
J Ahlner ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Stereoselective Pharmacokinetics

Estimation of 15O PET in healthy volunteers with automated ROI analysis by FineSRT

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S673-S673
Author(s):  
Ryo Takeuchi ◽  
Keiichi Matsumoto ◽  
Setsu Sakamoto ◽  
Yuhji Nakamoto ◽  
Michio Senda
Keyword(s):  
Healthy Volunteers
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