Phenotypic polymorphism and gender‐related differences of CYP1A2 activity in a Chinese population

Ouyang, Dongsheng; Huang, Shiyang; Wang, Wei; Xie, Hong‐Guang; Xu, Zhenhua; Shu, Yan; Zhou, Hong‐Hao

doi:10.1046/j.1365-2125.2000.00128.x

Cited by 106 publications

(80 citation statements)

References 40 publications

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“…A 16-fold interindividual variability in CYP1A2 activity has been observed in the Chinese population [11]. These results re¯ect the high variability of CYP1A2 activity in humans, which is dependent on environmental covariates [13] and possibly additional genetic factors [11,14]. The PAX/CAF ratio was reduced in elderly compared with young volunteers (Table 2) con®rming previous in vivo [15,16] and in vitro studies [17].…”

Section: Discussionsupporting

confidence: 77%

“…However in healthy nonsmokers only a 4-fold variability was observed [8]. A 16-fold interindividual variability in CYP1A2 activity has been observed in the Chinese population [11]. These results re¯ect the high variability of CYP1A2 activity in humans, which is dependent on environmental covariates [13] and possibly additional genetic factors [11,14].…”

Section: Discussionmentioning

confidence: 99%

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Variability of cytochrome P450 1A2 activity over time in young and elderly healthy volunteers

Simon

Becquemont

Hamon

et al. 2001

Brit J Clinical Pharma

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Aims To assess the age-associated changes over time of plasma paraxanthine/caffeine (PAX/CAF) ratios used as a probe for CYP1A2 activity. Methods Intraindividual and interindividual variabilities in PAX/CAF ratio were compared by phenotyping with caffeine, 16 young and 16 elderly healthy subjects on ®ve occasions. Results PAX/CAF ratio variability was comparable regardless of age (intraindividual CV: 17.6t6% and 16.2t5.9%, interindividual CV: 48.1t2.9% and 42.7t3.6% in young and elderly, respectively). The PAX/CAF ratio was lower in elderly than in young subjects (95% CI for the difference: 0.004, 0.32) but the difference was not signi®cant in nonsmokers compared separately. Conclusions The variability over time of the PAX/CAF ratio is not in¯uenced by age.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Variability of cytochrome P450 1A2 activity over time in young and elderly healthy volunteers

Simon

Becquemont

Hamon

et al. 2001

Brit J Clinical Pharma

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“…Thus, interindividual variability in CYP1A2 activity may alter the pharmacokinetics of these medications and influence response to therapy, including toxicities such as tardive dyskinesia with older (typical) antipsychotics (Carrillo et al, 2000;Kelly et al, 1999;Basile et al, 2000;Ou-Yang et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Correlation of Cytochrome P450 (CYP) 1A2 Activity Using Caffeine Phenotyping and Olanzapine Disposition in Healthy Volunteers

Shirley

Hon

Penzak

et al. 2002

Neuropsychopharmacol

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Olanzapine has previously been shown to have predominant metabolism by cytochrome (CYP) P450 1A2. Caffeine has been shown to provide an accurate phenotypic probe for measuring CYP1A2 activity. The purpose of this study is to determine if a significant correlation exists between olanzapine disposition and caffeine metabolic ratios. Subjects were phenotyped for CYP1A2 activity with caffeine probe methodology. After 200-mg caffeine administration, blood (4 h), saliva (6 and 10 h), and urine (8 h total) were collected for highperformance liquid chromatography (HPLC) analysis of caffeine and its metabolites.CYP1A2 activity was measured as plasma (PMR 4 h ), saliva (SMR 6 h and SMR 10 h ), and three urinary metabolic (UMR1 8 h , UMR2 8 h , and UMR3 8 h ) ratios. Each of the 14 healthy nonsmokers (13 male) received a single 10 mg olanzapine dose after which blood was collected for HPLC determination of olanzapine concentrations at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 h postdose. Olanzapine pharmacokinetic parameters in this study were similar to those previously published. All caffeine metabolic ratios (PMR 4 h , SMR 6 h , SMR 10 h , UMR1 8 h , and UMR2 8 h ) significantly correlated with each other (po0.001) except for UMR3 8 h , which did not correlate. A significant correlation (po0.05) was also found between olanzapine clearance and PMR 4 h (r ¼ 0.701), SMR 6 h (r ¼ 0.644), SMR 10 h (r ¼ 0.701), UMR1 8 h (r ¼ 0.745), and UMR2 8 h (r ¼ 0.710). A negative correlation was observed between olanzapine clearance and UMR3 8 h (r ¼ À0.029, p ¼ NS). A significant correlation was found between olanzapine clearance and various caffeine metabolic ratios. Interpatient variability in CYP1A2 activity may explain the wide interpatient variability in olanzapine disposition. Compounds that modulate CYP1A2 activity may be expected to alter olanzapine pharmacokinetics accordingly.

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“…The ratio of paraxanthine to caffeine at 6 h was reported to reflect the activity of CYP1A2 (Ou- Yang et al 2000). However, the information from a series of blood samples presenting the whole pharmacokinetics profile of caffeine and paraxanthine could demonstrate the results more comprehensively compared with a single blood sample, and provide a full view of the pharmacokinetics alteration of caffeine and paraxanthine by STS by affecting the activity of CYP1A2.…”

Section: Discussionmentioning

confidence: 96%

Effect of sodium tanshinone II A sulfonate on the activity of CYP1A2 in healthy volunteers

Chen

et al. 2009

Xenobiotica

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Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a famous Chinese medicine which has been used in the treatment of cardiovascular disorders for many years. Using caffeine as a probe drug, this project was designed to investigate the effect of STS on the activity of CYP1A2 in humans. Sixteen unrelated healthy volunteers were recruited for this two-phase, randomized and crossover study. The volunteers received either placebo or 60 mg day(-1) of STS injections through vein for 13 days. Pharmacokinetics of caffeine and the metabolite paraxanthine was determined by high-performance liquid chromatography. CYP1A2 activity was monitored by the ratio of paraxanthine to caffeine at 6 h in plasma. Enzyme activity analysis showed that STS significantly increased the activity of CYP1A2 by 41.1% [90% confidence interval (CI), 17.4-64.8%] (p = 0.036). The area under the curve [AUC((0-24h))] of caffeine significantly decreased by 13.3% [90% CI = 7.0-19.6%] (p = 0.005) with 13 days of treatment of STS. AUC((0-24h)) of paraxanthine significantly increased by 17.4% [90% CI = 4.3-30.5%] (p = 0.035). No significant difference was found for other parameters of caffeine and paraxanthine between two phases. STS has significantly induced the activity of CYP1A2 in vivo. Simultaneously, AUC((0-24h)) of caffeine and paraxanthine were significantly affected by STS. The findings have provided some useful information for safe and effective usage of STS in clinic.

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Phenotypic polymorphism and gender‐related differences of CYP1A2 activity in a Chinese population

Cited by 106 publications

References 40 publications

Variability of cytochrome P450 1A2 activity over time in young and elderly healthy volunteers

Variability of cytochrome P450 1A2 activity over time in young and elderly healthy volunteers

Correlation of Cytochrome P450 (CYP) 1A2 Activity Using Caffeine Phenotyping and Olanzapine Disposition in Healthy Volunteers

Effect of sodium tanshinone II A sulfonate on the activity of CYP1A2 in healthy volunteers

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