Track topics on Twitter Track topics that are important to you
Background Cytochrome P450s (CYPs, EC 188.8.131.52) 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.
This article was published in the following journal.
Name: Drug metabolism and personalized therapy
Carnitine is an essential molecule for mitochondrial beta-oxidation of long-chain fatty acids and other cellular functions. Several rare, inherited disorders of carnitine metabolism occur in humans, a...
Although previous data indicate that dyadic coping is associated with Hypothalamic-Pituitary-Adrenal (HPA-axis and C-reactive protein (CRP) separately, no study has reported on the ratio between these...
The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute...
Patients on hemodialysis (HD) are known to be at risk of carnitine deficiency. The aims of this study were to investigate the prevalence of carnitine deficiency in patients on dialysis and to compare ...
There is conflicting data on whether variations of physiologic cortisol levels associate with cardiovascular risk. We hypothesize that prior discordant findings are related to problems associated with...
This study is being conducted to obtain information on the safety and tolerability of repeated doses of GW823296 for 28 days in healthy male and female subjects. In addition, the pharmacok...
Recently, McLean hospital conducted a 4 month taurine study which showed a reduction in mania ratings. As a follow-up to the preliminary taurine study, and complementary to the currently o...
The purpose of this study is to determine whether Taurine 4g is effective with antipsychotic medication in the treatment of First Episode Psychosis.Taurine may have an effect on cognition ...
Diabetes has become important risk factors for threatening human life and health. Lower extremity arterial occlusive are the common complications of diabetes.Sulfur amino acid is the indis...
the results from animal studies and preliminary human studies show that carnitine availability and acetylcarnitine concentrations are low in insulin resistant states such as with type 2 di...
An enzyme that catalyzes the formation of O-acetylcarnitine from acetyl-CoA plus carnitine. EC 184.108.40.206.
The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.
A high-affinity, ATP-binding, co-transporter for CARNITINE that is highly expressed in kidney, skeletal muscle, heart, and placental tissues. It transports one sodium ion with one carnitine molecule. It has a lower affinity for other organic cations and transports them independently of sodium. Mutations in the SLC22A5 gene are associated with systemic carnitine deficiency.
Acyltransferases in the inner mitochondrial membrane that catalyze the reversible transfer of acyl groups from acyl-CoA to L-carnitine and thereby mediate the transport of activated fatty acids through that membrane. EC 2.3.1.
An enzyme that catalyzes the HYDROXYLATION of gamma-butyrobetaine to L-CARNITINE. It is the last enzyme in the biosynthetic pathway of L-CARNITINE and is dependent on alpha-ketoglutarate; IRON; ASCORBIC ACID; and OXYGEN.
Benign Prostatic Hyperplasia (BPH) Erectile Dysfunction Urology Urology is the branch of medicine concerned with the urinary tract and diseases that affect it. Examples include urethritis, urethrostenosis and incontinence. Urology is a su...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...