Comparative pharmacogenetics of sparteine and debrisoquine. by Alexander Antonius Matheus Vinks

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Number of Pages65
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Capacities to oxidize sparteine and debrisoquine in healthy Canadian Caucasians were compared. The Spearman rank correlation between the conventional urinary metabolic ratios (drug/metabolite) was r s = (P sparteine metabolic ratio appears to be the more discriminating probe to distinguish metabolizers and nonmetabolizers.

The urinary amount of oxidized sparteine alone may Cited by: Comparative pharmacogenetics of sparteine and debrisoquine Capacities to oxidize sparteine and debrisoquine in healthy Canadian Caucasians were compared.

The urinary amount of oxidized sparteine alone may allow reliable detection of nonmetabolizers. From a total of 17 poor metabolizers observed in this study and in studies in Germany and Sweden, all were deficient in metabolizing capacity for both sparteine and by:   The urinary amount of oxidized sparteine alone may allow reliable detection of nonmetabolizers.

From a total of 17 poor metabolizers observed in this study and in studies in Germany and Sweden, all were deficient in metabolizing capacity for both sparteine and by: Inaba T, Vinks A, Otton SV, Kalow () Comparative pharmacogenetics of sparteine and debrisoquine. Clin Pharmacol Ther Evans DAR Harmer D, Downham DY, Whibley E J, Idle JR, Ritchie J, Smith RL () The genetic control of sparteine and M.

Veronese and S. McLean: Genetic polymorphism in Tasmanian debrisoquine metabolism in. European data on the polymorphic metabolism of debrisoquine, sparteine, dextromethorphan and mephenytoin have been collected. No significant difference in phenotype frequencies was found between the separate series for debrisoquine, sparteine and dextromethorphan, which supports the claim that these probe drugs reflect the same enzyme by: Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity Article Literature Review (PDF Available) in Pharmacogenomics 10(1) February with Reads.

Pharmacogenetics and pharmacogenomics are two disciplines with overlapping aims, the latter newer and broader than the former. A search of PubMed revealed more than hits for pharmacogenetics Cited by: The genetic control of sparteine and debrisoquine metabolism in man with new methods of analysing bimodal distributions.

J Med Genet. Oct; 20 (5)– [Europe PMC free article] [Google Scholar] Inaba T, Vinks A, Otton SV, Kalow W. Comparative pharmacogenetics of sparteine and debrisoquine. Clin Pharmacol Ther. Mar; 33 (3)– UNESCO – EOLSS SAMPLE CHAPTERS PHARMACOLOGY – Vol. I - Pharmacogenomics and Pharmacogenetics - Andrew A Somogyi and Janet K Coller ©Encyclopedia of Life Support Systems (EOLSS) role and importance that pharmacogenetics can play in the pharmacokinetics (metabolism and transport) and inherent pharmacodynamic properties of drugs.

Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism () Comparative pharmacogenetics of sparteine and debrisoquine. Clin Pharmacol Ther – Brøsen, K., Klysner, R., Gram, L.F.

et al. Steady-state concentrations of imipramine and its metabolites in relation to Cited by: The debrisoquine hydroxylation phenotype was studied in unselected healthy Tasmanian subjects, who were mostly Caucasians of British ancestry. Following a 10 mg oral dose of debrisoquine (D), the ratio of D/4-hydroxydebrisoquine excreted in 8-h urine (metabolic ratio, MR) was determined.

MR values were bimodally by:   CYP2D6 genotype and debrisoquine metabolic ratio (MR) were analyzed in Nicaraguan Mestizos (NMs) and Cubans divided into Cuban Mestizos (CMs) and White Cubans (WCs). The frequencies of Cited by: The study of pharmacogenetics and pharmacogenomics focuses on how our genes and complex gene systems influence our response to drugs.

Recent progress in the science of clinical therapeutics has led to the discovery of new biomarkers that make it technically easier to identify groups of patients which are more or less likely to respond to individual therapies/5(2). Eichelbaum M, Gross AS () The genetic polymorphism of debrisoquine sparteine metabolism—clinical aspects.

In: Kalow W (ed) Pharmacogenetics of drug metabolism. Pergamon, New York, pp – Google ScholarCited by: 1. Inaba T, Vinks A, Otton SV, Kalow W. Comparative pharmacogenetics of sparteine and debrisoquine.

Clin Pharmacol Ther. Mar; 33 (3)– Inaba T, Jurima M, Mahon WA, Kalow W. In vitro inhibition studies of two isozymes of human liver cytochrome P Mephenytoin p-hydroxylase and sparteine monooxygenase. Drug Metab by: Debrisoquine and sparteine tests were carried out in random white British subjects.

There is a high degree of correlation between the urinary 'metabolic ratios' of the two drugs. The molecular mechanism of the debrisoquine/sparteine polymorphism was discovered a few years later.

Biochemical studies in human liver microsomes first indicated that a Cited by: Concluding comments. The study of pharmacogenetics and ecogenetics among different individuals and populations offers an unique opportunity to understand multiple, simultaneously occurring interactions between genes and the environment, and the subsequent phenotypic expression of Cited by: Inaba T, Vinks A, Otton SV, Kalow W.

Comparative pharmacogenetics of sparteine and debrisoquine. Clin Pharmacol Ther. Mar; 33 (3)– Lennard MS, Tucker GT, Silas JH, Woods HF.

Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. Xenobiotica.

May; 16 (5)– The P enzyme responsible for the debrisoquine/sparteine polymorphism is CYP2D6, a Phase I enzyme. Cloning of the CYP2D6 genes and characterization of several mutant alleles (47) represented a landmark study providing for the first time a molecular mechanism to explain a descriptive pharmacogenetics disorder.

PM alleles can code for an inactive enzyme because of mutation. Inaba T, Vinks A, Otton SV, Kalow W. Comparative pharmacogenetics of sparteine and debrisoquine. Clin Pharmacol Ther. Mar; 33 (3)– [Google Scholar] Inaba T, Jurima M, Mahon WA, Kalow W.

In vitro inhibition studies of two isozymes of human liver cytochrome P Mephenytoin p-hydroxylase and sparteine by: Abstract. A simple borohydride/GC method was developed for phenotyping sparteine oxidation in man.

The major metabolites of sparteine found in human urine, 2- and 5-dehydrosparteine, were converted quantitatively back to sparteine by sodium borohydride reduction. The major metabolites of sparteine found in human urine, 2- and 5-dehydrosparteine, were converted quantitatively back to sparteine by sodium borohydride reduction.

The amount of sparteine metabolites can be estimated from the difference of sparteine concentrations between the borohydride-treated and untreated urine by: 3. Four different mutations of the cytochrome P CYP2D6 gene associated with the poor metabolizer phenotype (PM) of the debrisoquine/sparteine polymorphism were analyzed by Xba I restriction fragment length polymorphism (RFLP) analysis and a polymerase chain reaction (PCR)-based DNA amplification method in DNA of healthy European subjects; of these were phenotyped by sparteine Cited by: Polymorphic oxidation of the pharmacogenetic probe drug sparteine was investigated in 35 parents and 29 siblings of 20 unrelated poor metabolizer (PM) probands.

Phenotyping was carried out on the basis of metabolic ratio (MR) = sparteine/dehydrosparteines in the 12 h by: CYP2D6 pharmacogenomics.

prototypical substrates of CYP2D6 are debrisoquine and sparteine. Many have remained central elements over the 18 years that span the three editions of this book.

The P enzyme responsible for the debrisoquine/sparteine polymorphism is CYP2D6, a Phase I enzyme. Cloning of the CYP2D6 genes and characterization of several mutant alleles (47) represented a landmark study providing for the first time a molecular mechanism to explain a descriptive pharmacogenetics disorder.

Inaba T, Jurima M, Nakano M, Kalow W. Mephenytoin and sparteine pharmacogenetics in Canadian Caucasians. Clin Pharmacol Ther. Nov; 36 (5)– Inaba T, Vinks A, Otton SV, Kalow W. Comparative pharmacogenetics of sparteine and debrisoquine. Clin Pharmacol Ther.

Cited by: In this review I have attempted to summarize gender differences in pharmacokinetics involving the cytochrome P (CYP) isozymes of young and mature adults, excluding the effectsCited by:   A subsequent study with 10 mg debrisoquine in 94 subjects identified the two phenotypes.

17 Michel Eichelbaum in Bonn studied the antiarrhytmic effects of sparteine and two subjects complained Cited by: The P enzyme responsible for the debrisoquine/sparteine polymorphism is CYP2D6, a Phase I enzyme.

Cloning of the CYP2D6 genes and characterization of several mutant alleles (47) represented a landmark study providing for the first time a molecular mechanism to explain a descriptive pharmacogenetics disorder.

PM alleles can code for an. Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ. Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol. ;16(3) Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL. Polymorphic hydroxylation of debrisoquine in man.

Eight healthy volunteers received oral metoprolol mg once daily for a week. The AUC, half‐life and duration of beta‐adrenoceptor blockade on day 7 was much greater in two subjects than in the rem Cited by: At about the same time, an inborn defect of the metabolism of a drug called debrisoquine was found in England[10] and of the drug sparteine in Germany.[11] Our laboratory,[12] like a Swedish laboratory,[13] compared these 2 defects in some people.

At about the same time, an inborn defect of the metabolism of a drug called debrisoquine was found in England[10] and of the drug sparteine in Germany.[11] Our laboratory,[12] like a Swedish laboratory,[13] compared these 2 defects in some people.

Pharmacogenomics is the study of the role of the genome in drug response. Its name (pharmaco-+ genomics) reflects its combining of pharmacology and cogenomics analyzes how the genetic makeup of an individual affects his/her response to drugs.

It deals with the influence of acquired and inherited genetic variation on drug response in patients by correlating gene expression or. E-Mail Address. Password. Forgotten Password. Remember Me. Most antipsychotics and antidepressants are also metabolized by CYP2C19 (polymorphic mephenytoin hydroxylase) and/or CYP2D6 (polymorphic debrisoquine/sparteine hydroxylase).

In the present review, we will discuss clinically significant pharmacokinetic drug interactions involving antidepressants, but excluding benzodiazepines (18) and Cited by: isfactorily.

A systematic sequencing strategy through kb of the CYP2D6 5 ′-flanking sequence revealed six mutations of which three were exclusively associated with the functional CYP2D6*2 allele (− C to G;− C to T; and − G to A), two were associated with the nonfunctional *4 and with the functional *alleles (− C to T and − G to A) and one (− A to.

The incidence of poor metabolizers (PM) of debrisoquine/sparteine with deficient CYP2D6 activity has been investigated in many populations, in most of them with a fairly small number of subjects [13, 14]. Among Swedish Caucasians we found 69 (%) PM of by: A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text.Cytochrome P 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene.

CYP2D6 is primarily expressed in the is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D6, a member of the cytochrome P mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in Aliases: CYP2D6, CPD6, CYP2D, CYP2D7AP.

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