The influence of enzyme induction on polymorphic sparteine oxidation.

Eichelbaum, Michel; Mineshita, Satoru; Ohnhaus, E. E.; Zekorn, C

doi:10.1111/j.1365-2125.1986.tb02879.x

Cited by 86 publications

(42 citation statements)

References 15 publications

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“…Furthermore, it is known that CYP2D6 is not easily induced. Rifampin, which is a strong inducer, decreases plasma levels of CYP2D6 substrates by only approximately 25% (5,11). Our trial showed a decrease in paroxetine AUC 0-24 of 55%.…”

Section: Discussionmentioning

confidence: 70%

Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects

Lee

Blenke

Rongen

et al. 2007

Antimicrob Agents Chemother

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Human immunodeficiency virus-infected patients have an increased risk for depression. Despite the high potential for drug-drug interactions, limited data on the combined use of antidepressants and antiretrovirals are available. Theoretically, ritonavir-boosted protease inhibitors may inhibit CYP2D6-mediated metabolism of paroxetine. We wanted to determine the effect of fosamprenavir-ritonavir on paroxetine pharmacokinetics and vice versa and to evaluate the safety of the combination. Group A started with 20 mg paroxetine every day for 10 days; after a wash-out period of 16 days, subjects received paroxetine (20 mg every day) plus fosamprenavir-ritonavir (700/100 mg twice a day) from days 28 to 37. Group B received the regimens in reverse order. On days 10 and 37, pharmacokinetic curves were recorded. Twenty-six healthy subjects ( t 1/2 ). The free fraction of paroxetine showed a median (interquartile range) increase of 30% (18 to 42%) after the addition of fosamprenavir-ritonavir. The AUC 0-12 , C max , C min , and t 1/2 of amprenavir and ritonavir were similar to those of historical controls. No serious adverse events occurred. Fosamprenavirritonavir reduced total paroxetine exposure by 55%. This is partly explained by protein displacement of paroxetine. We think that this interaction is clinically relevant and that titration to a higher dose of paroxetine may be necessary to accomplish the needed antidepressant effect.

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Section: Discussionmentioning

confidence: 70%

Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects

Lee

Blenke

Rongen

et al. 2007

Antimicrob Agents Chemother

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“…(2) (Bax et al, 1981;Brinn et al, 1986;Eichelbaum et al, 1986). This concept of nonadditivity of environmental factors is well recognized by some geneticists who refer to a norm-of-reaction between the environment and the genotype (Suzuki et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Testing for bimodality in frequency distributions of data suggesting polymorphisms of drug metabolism‐histograms and probit plots.

Jackson

Tucker

Woods

1989

Brit J Clinical Pharma

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1. The shape of histograms used to illustrate density distributions of indices of polymorphic drug metabolism was shown to be sensitive to the position of the cell divisions. 2. Non‐linearity of the probit plot was shown not to indicate bimodality of the original density distribution. Computer simulation was used to generate examples of unimodal density distributions with curvilinear probit plots. 3. Using the same technique probit plots for bimodal density distributions were constructed. Some were shown to differ less from the probit plots of certain unimodal distributions than did the original density distributions. 4. The position of the antimode was shown not to coincide with inflections seen in the probit plots. 5. A new method for determining the linearity of probit plots is suggested.

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“…CYP2D6*10 is responsible for the reduced enzyme activity in IMs whereas CYP2D6*4, CYP2D6*5 and CYP2D6*14 are null alleles which encode no enzyme at all. UM (CYP2D6*xN) has a duplication or multiduplication of functional alleles and leads to increase enzymes activity (6)(7)(8). This variation causes variability in patients' outcomes because CYP2D6 had been reported to biotransform tamoxifen into several active metabolites.…”

Section: Introductionmentioning

confidence: 99%

The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

Teh

Mohamed

Salleh

et al. 2011

AAPS J

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Abstract. CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of Pglycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P=0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P=0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI=0.79-23.2) compared to those without this combination which was 48 months (95% CI=14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.KEY WORDS: ABCB1; breast cancer; CYP2D6; recurrence and metastasis; tamoxifen.

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The influence of enzyme induction on polymorphic sparteine oxidation.

Cited by 86 publications

References 15 publications

Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects

Interaction Study of the Combined Use of Paroxetine and Fosamprenavir-Ritonavir in Healthy Subjects

Testing for bimodality in frequency distributions of data suggesting polymorphisms of drug metabolism‐histograms and probit plots.

The Risk of Recurrence in Breast Cancer Patients Treated with Tamoxifen: Polymorphisms of CYP2D6 and ABCB1

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