High interindividual variability in plasma clopidogrel active metabolite concentrations in healthy cats is associated with sex and cytochrome P450 2C genetic polymorphism

2018 ◽  
Vol 42 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Pamela M. Lee ◽  
Michele C. L. Faus ◽  
Michael H. Court
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphism ◽  
Active Metabolite ◽  
Interindividual Variability ◽  
Cytochrome P450 2C ◽  
Metabolite Concentrations ◽  
High Interindividual Variability

Associations of CYP2A6 Gene Polymorphism with Smoking Status Among Jordanians: Gender-Related Differences

2019 ◽  
Vol 20 (9) ◽  
pp. 765-770 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Belal Azab ◽  
Al M. Best ◽  
Yousef S. Khader ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphism ◽  
Smoking Status ◽  
Hepatic Enzyme ◽  
Nicotine Metabolism ◽  
Significant Frequency ◽  
Cytochrome P450 2A6 ◽  
Study Population ◽  
Major Metabolic Pathway ◽  
Cyp2a6 Gene

Background: Cytochrome P450 2A6 enzyme (CYP2A6), an essential hepatic enzyme involved in the metabolism of drugs, is responsible for a major metabolic pathway of nicotine. Variation in the activity of polymorphic CYP2A6 alleles has been implicated in inter-individual differences in nicotine metabolism. Aims: The objective of the current study was to assess the association between the smoking status and the cytochrome P450 2A6 enzyme (CYP2A6) genotype in Jordanians. Methods: In the current study, 218 (117 Male and 101 female) healthy unrelated Jordanian volunteers were recruited. CYP2A6*1B, CYP2A6*4 and CYP2A6*9 were determined and correlated with subject smoking status. Results: *1A/*1A was the most common genetic polymorphism in the overall study population, with no significant frequency differences between smokers and non-smokers. When the population was divided according to gender, only male smokers showed a significant correlation between genotype and smoking status. Considering the CYP2A6*9 genotype, the results showed differences in distribution between smokers and non-smokers, but only women showed a significant association between CYP2A6*9 allele genotype and smoking status. Conclusion: The results of this study show that there is a significant association between CYP2A6*9 genotype and smoking status. They also show that CYP2A6 genotype is significantly influenced by gender.

scholarly journals Exploring the effect of khat (Catha edulis) chewing on the pharmacokinetics of the antiplatelet drug clopidogrel in rats using the newly developed LC-MS/MS technique

2020 ◽  
Vol 18 (1) ◽  
pp. 681-690
Author(s):  
Hassan A. Alhazmi ◽  
Adnan A. Kadi ◽  
Mohamed W. Attwa ◽  
Waquar Ahsan ◽  
Manal Mohamed Elhassan Taha ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Metabolite ◽  
Dose Adjustment ◽  
Internal Standard ◽  
Cardiovascular Complications ◽  
Antiplatelet Drug ◽  
Peak Ratio ◽  
Cytochrome P450 Enzymes ◽  
Time Intervals ◽  
Addictive Substance

AbstractClopidogrel (CLOP) is widely used worldwide for cardiovascular complications. CLOP is highly metabolized in the liver to its active metabolite by cytochrome P450 enzymes. Studies have shown that khat, an addictive substance, is a powerful inhibitor of cytochrome P450 enzymes and can influence the metabolism of drugs that are concomitantly used. Therefore, this study was designed to evaluate the effects of khat on the pharmacokinetics of CLOP in rats. In this study, rats were administered either CLOP alone or CLOP combined with khat and their plasma were obtained at different time intervals and analyzed using the newly developed and validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method using foretinib (FTB) as the internal standard. The corresponding peak area of the analyte versus FTB was used for calculating the peak ratio. The validated LC-MS/MS method resulted in the separation of the well-defined quantifiable peaks of CLOP, FTB, and CLOP metabolite within 7 min. Results showed a significant influence of khat on the peak ratio of CLOP metabolite, which was found to be significantly decreased (P < 0.05) in comparison to CLOP alone, suggesting significant decrease in the conversion of CLOP to its active metabolite due to the inhibition of CYP450 enzymes by khat. Therefore, there might be a need for dose adjustment for regular khat chewers using CLOP.

scholarly journals Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report

2021 ◽  
Vol 22 (12) ◽  
pp. 6480
Author(s):  
Céline K. Stäuble ◽  
Markus L. Lampert ◽  
Thorsten Mikoteit ◽  
Martin Hatzinger ◽  
Kurt E. Hersberger ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Case Report ◽  
Adverse Drug Reactions ◽  
Active Metabolite ◽  
Hepatic Metabolism ◽  
Cytochrome P450 3A4 ◽  
Drug Reactions ◽  
Drug Induced ◽  
Potential Impact ◽  
Intermediate Metabolizer

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient’s pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.

Saliva and serum testosterone following oral testosterone undecanoate administration in normal and hypogonadal men

1983 ◽  
Vol 102 (3) ◽  
pp. 456-462 ◽  
Author(s):  
Th. Schürmeyer ◽  
E. J. Wickings ◽  
C. W. Freischem ◽  
E. Nieschlag
Keyword(s):  
Interindividual Variability ◽  
Serum Testosterone ◽  
Serum Samples ◽  
Additional Increase ◽  
Testosterone Undecanoate ◽  
Absorption Pattern ◽  
High Interindividual Variability ◽  
Normal Men ◽  
Hydrolysis Of ◽  
Testosterone Ester

Abstract. Since saliva testosterone reflects the testosterone fraction available to target tissues the therapeutic effectiveness of orally administered testosterone undecanoate was assessed by measuring testosterone in serum and saliva. Matched saliva and serum samples were obtained from 12 normal men and 8 hypogonadal men before and at hourly intervals after the oral administration of 120 mg testosterone undecanoate. The test was repeated in 3 men after they had taken 40 mg testosterone undecanoate twice daily for 4 to 5 weeks. Following testosterone undecanoate administration serum and saliva testosterone always showed parallel increases. However, the absorption curves showed a high interindividual variability in the time when maximum concentrations were reached, as well as in the maximum levels themselves. The increases in serum and saliva testosterone were similar in normal and hypogonadal men. In normal men basal levels were reached 4 h after the maximum had occurred, while in hypogonadal men testosterone levels were not different from basal levels 2 h after the maximum. The study shows that testosterone undecanoate is well absorbed from the gut and releases significantly elevated amounts of testosterone which is available to target tissues. As the absorption pattern was always parallel in both fluids, hydrolysis of the circulating testosterone ester by the tissue ifself seems to effect no additional increase of testosterone in the tissue.

Plasma Levels of 25-Hydroxyvitamin D3andIn VivoMarkers of Cytochrome P450 3A Activity in Swedes and Koreans: Effects of a Genetic Polymorphism and Oral Contraceptives

2014 ◽  
Vol 115 (4) ◽  
pp. 366-371 ◽  
Author(s):  
Hanna Nylén ◽  
Linda Björkhem-Bergman ◽  
Lena Ekström ◽  
Hyung-Keun Roh ◽  
Leif Bertilsson ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphism ◽  
Oral Contraceptives ◽  
Plasma Levels ◽  
Cytochrome P450 3A
Sign in / Sign up

Export Citation Format

Share Document