Effects of functional CYP2C8,CYP2C9,CYP3A5,and ABCB1 genetic variants on the pharmacokinetics of insulin sensitizer pioglitazone in Chinese Han individuals

Yin, Sheng-Ju; Qi, Huimin; Wang, Xin; Zhang, Pu; Lü, Yuan; Wei, Min-Ji; Li, Pu; Qi, Guangzhao; Lou, Ya-Qing; Lu, Chuang; Zhang, Guoliang

doi:10.1097/fpc.0000000000000265

Cited by 3 publications

(3 citation statements)

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“…Twenty-four healthy male Chinese Han ethnic volunteers were recruited for the mizolastine pharmacokinetics evaluation. The mean age, average weight and body mass index of the 24 volunteers were 25.60 (22)(23)(24)(25)(26)(27)(28)(29) years old, 65.71 (58-80) kg and 22.12 (19.51-21.15) kg/m 2 , respectively. All of them were non-smokers and in good health as evaluated by physical examination and laboratory evaluation before entering the study.…”

Section: Methodsmentioning

confidence: 99%

“…ABCB1 gene encodes P-glycoprotein (P-gp, or multidrug-resistance protein 1, MDR1). One of the most widely studied functional SNPs in ABCB1 gene is C3435T (rs1045642, ILe 1145ILe) in exon 26 [25], which also has a higher frequency in Chinese population than that in other ethnic groups including Caucasian and African populations [26][27][28]. Other research groups have reported of a correlation between genetic polymorphisms of allergic response proteins, such as IgE receptor (FCERIA) and component 5a receptor 1 (C5AR1), and the therapeutic efficacy or side effects of mizolastine in vivo [29][30][31].…”

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confidence: 99%

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Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

Wei

Zhang

et al. 2018

Basic Clin Pharma Tox

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Mizolastine is a selective histamine H1 receptor antagonist for chronic urticaria or allergic rhinitis. We investigated whether the variant genotypes of metabolic enzymes UGT1A1, CYP3A5 and transporter ABCB1 influence pharmacokinetic phenotype of substrate mizolastine in Chinese volunteers. Genotyping of single nucleotide polymorphisms in UGT1A1*6 (G211A), CYP3A5*3 (A6986G) and ABCB1 (C3435T) was determined by the pyrosequencing method. After a single oral dose of 10 mg mizolastine, the plasma concentrations were measured using validated high-performance liquid chromatography in 24 Chinese healthy volunteers. The results showed that the distributions of wild-type homozygotes and variant allele carriers (the sum of variant heterozygotes and variant homozygotes) were as follows: 17 cases (70.8%) versus seven cases (29.2%) in UGT1A1*6 genotypes, five cases (20.8%) versus 19 cases (79.2%) in CYP3A5*3 genotypes and seven cases (29.2%) versus 17 cases (70.8%) in ABCB1 3435T genotypes, respectively. There were no significant differences in pharmacokinetic parameters of mizolastine between the variant allele UGT1A1*6, CYP3A5*3 and ABCB1 3435T carriers and the wild-type homozygotes, and the ratios were as follows: C was 101.03%, 86.02% and 105.78%; T was 162.35%, 98.98% and 144.90%; AUC was 113.04%, 77.35% and 112.71%; and t was 95.77%, 72.40% and 100.97%, respectively. In conclusion, these results suggested that the UGT1A1, CYP3A5 and ABCB1 genetic polymorphisms might be not contributed to the interindividual variation of mizolastine pharmacokinetic phenotype in the Chinese population.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

Wei

Zhang

et al. 2018

Basic Clin Pharma Tox

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“…Cytochrome P‐450 (CYP)2C9 is the major enzyme responsible for AZL metabolism. Because the frequency of CYP2C9 polymorphic alleles shows marked interethnic variation, AZL pharmacokinetics may also differ among people of different ethnicities; indeed, such variation has been observed in the case of other CYP2C9 substrates such as pioglitazone . However, thus far, the pharmacokinetics of AZL in the Chinese population has not been investigated.…”

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confidence: 99%

Clinical Evaluation of the Tolerability and Pharmacokinetics of Azilsartan, a Potent Angiotensin Receptor Blocker, in Healthy Chinese Subjects

Liu

Sheng

et al. 2019

Clinical Pharm in Drug Dev

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Azilsartan (AZL), the active metabolite of azilsartan medoxomil, is the newest angiotensin receptor blocker that has been approved for the treatment of hypertension in 2012 in Japan. The present study aimed to evaluate the safety and pharmacokinetic properties of AZL in healthy Chinese subjects. We performed 2 phase 1 studies to investigate the pharmacokinetics and safety of AZL in healthy Chinese adults after a single dose (20 mg or 40 mg) or multiple doses of AZL (40 mg/d for 7 days; Study I) and after a single 40-mg dose under the fasted and fed conditions (Study II). Noncompartmental analysis and nonlinear mixed-effects modeling were used to analyze the pharmacokinetic properties of AZL. Twenty-seven healthy volunteers (14 men and 13 women) aged 20-32 years were enrolled and completed the study. During single dosing of AZL, the pharmacokinetics of AZL exhibited a linear profile between dosage and area under the concentration-time curve. There is no AZL accumulation after multiple doses. Food had no effect on the pharmacokinetic characteristics of AZL. AZL concentrations were best fit with a 2-compartment model, and the typical value of clearance was 1.63 L/h. Body weight had an impact on both the apparent clearance and peripheral volume of distribution. The pharmacokinetic parameters were consistent with previous studies in non-Chinese subjects. Modelbased simulations indicated that a 45-kg subject would have approximately double the AZL exposure of a 90-kg subject. Whether the exposure difference has clinical significance needs to be confirmed in further studies among patients.Azilsartan (AZL), the active moiety of azilsartan medoxomil, is an angiotensin receptor blocker. In 2012 AZL was approved for the treatment of hypertension in Japan. For the management of hypertension, AZL should be administered at a dose of 20 mg once daily (maximum dose, 40 mg once daily) according to the label information for Azilva. [1][2][3] After oral administration, plasma concentrations of AZL peak within 1.8-2.4 hours, and the elimination half-life (t ½ ) is approximately 13 hours. 4 AZL is eliminated through both renal clearance and hepatic metabolism. 4 Its renal clearance is 0.138 L/h, and its apparent oral clearance is 1.5 L/h. AZL is highly bound to human plasma proteins (>99%), mainly serum albumin. The volume of distribution of AZL is approximately 16 L. The pharmacokinetic characteristics of AZL are practically identical to those of its prodrug azilsartan medoxomil. [4][5][6][7] Cytochrome P-450 (CYP)2C9 is the major enzyme responsible for AZL metabolism. Because the frequency of CYP2C9 polymorphic alleles shows

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Interaction between 3,4‑dichlorophenyl‑propenoyl‑sec.‑butylamine (3,4‑DCPB), an antiepileptic drug, and cytochrome P450 in rat liver microsomes and recombinant human enzymes in vitro

Cheng

Wang

et al. 2018

European Journal of Pharmaceutical Sciences

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Effects of functional CYP2C8,CYP2C9,CYP3A5,and ABCB1 genetic variants on the pharmacokinetics of insulin sensitizer pioglitazone in Chinese Han individuals

Cited by 3 publications

References 60 publications

Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

Clinical Evaluation of the Tolerability and Pharmacokinetics of Azilsartan, a Potent Angiotensin Receptor Blocker, in Healthy Chinese Subjects

Interaction between 3,4‑dichlorophenyl‑propenoyl‑sec.‑butylamine (3,4‑DCPB), an antiepileptic drug, and cytochrome P450 in rat liver microsomes and recombinant human enzymes in vitro

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