Effect of Organic Anion-Transporting Polypeptide 1B1 (OATP1B1) Polymorphism on the Single- and Multiple-Dose Pharmacokinetics of Enalapril in Healthy Chinese Adult Men
Enalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of th...
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| Published in | Clinical therapeutics Vol. 33; no. 5; pp. 655 - 663 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Bridgewater, NJ
Elsevier Inc
01.05.2011
Elsevier Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0149-2918 1879-114X 1879-114X |
| DOI | 10.1016/j.clinthera.2011.04.018 |
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| Abstract | Enalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of the OATP1B1 gene may play a role in causing the interindividual pharmacokinetic differences of this drug.
The purpose of this study was to investigate the functional significance of the OATP1B1 genetic polymorphism on the pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy Chinese adult male participants.
This was a single-center, open-label, single- and multiple-dose study conducted in healthy Chinese male participants. Each participant received a single oral dose of 10 mg enalapril under fasting conditions, followed by enalapril 10 mg/d for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 24 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7; on day 7, samples were collected from 0 to 72 hours after drug administration. An HPLC-MS/MS method was used to determine plasma concentrations of enalapril and enalaprilat. A polymerase chain reaction technique was used for genotyping of 2 single nucleotide polymorphisms (SNPs) of the OATP1B1 gene: T521C and A388G. The pharmacokinetic parameters of enalapril and enalaprilat were then compared according to genotype groups, using 1-way ANOVA, except for Tmax in which the Mann-Whitney test or Kruskal-Wallis test was used.
The study included 32 healthy Han Chinese male participants (age range, 18–28 years; weight range, 50.0–80.0 kg; height range,159–182.0 cm). Twenty-six were OATP1B1*15 noncarriers (homozygous for 521TT), the others were *15 carriers with at least one 521 T>C mutant allele. After single and multiple oral doses of 10 mg enalapril, plasma concentrations of enalapril in *15 noncarriers were lower than that in *15 carriers, with significant difference in area under the curve at steady state (AUCss) between *15 noncarriers and *15 carriers (P = 0.048) in the multiple-dose phase. There were no significant differences in enalapril's AUC0–24, Cmax, or the ratio of the AUC0–24h in the single-dose study to the AUCss (Rac) between the *15 carriers and noncarriers. In contrast to enalapril, the mean AUC0–24h and Cmax of enalaprilat in *15 noncarriers was significantly higher than those in *15 carriers (P = 0.040 and P = 0.027, respectively) in the single-dose phase. There were no significant differences in enalaprilat's AUCss or Cmaxss between the 2 groups in the multiple-dose phase. For the 3 groups classified according to the effect of A388G variant in all subjects homozygous for 521T (TT), *1a/*1a, *1a/*1b, and *1b/*1b, no significant difference was found in AUC0–24h, Cmax, and Tmax of enalapril and enalaprilat.
In this small population of healthy Chinese men, the OATP1B1*15 allele and T521C variant appeared to be an important determinant of the pharmacokinetics of enalapril. There were significant differences between the *15 carriers and noncarriers in enalapril's AUCss and enalaprilat's AUC0–24h, Cmax, and Rac. However, there were no significant differences in enalapril's AUC0–24, Cmax, or enalaprilat's AUCss, Cmaxss between the *15 carriers and noncarriers. |
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| AbstractList | Enalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of the OATP1B1 gene may play a role in causing the interindividual pharmacokinetic differences of this drug.
The purpose of this study was to investigate the functional significance of the OATP1B1 genetic polymorphism on the pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy Chinese adult male participants.
This was a single-center, open-label, single- and multiple-dose study conducted in healthy Chinese male participants. Each participant received a single oral dose of 10 mg enalapril under fasting conditions, followed by enalapril 10 mg/d for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 24 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7; on day 7, samples were collected from 0 to 72 hours after drug administration. An HPLC-MS/MS method was used to determine plasma concentrations of enalapril and enalaprilat. A polymerase chain reaction technique was used for genotyping of 2 single nucleotide polymorphisms (SNPs) of the OATP1B1 gene: T521C and A388G. The pharmacokinetic parameters of enalapril and enalaprilat were then compared according to genotype groups, using 1-way ANOVA, except for T(max) in which the Mann-Whitney test or Kruskal-Wallis test was used.
The study included 32 healthy Han Chinese male participants (age range, 18-28 years; weight range, 50.0-80.0 kg; height range,159-182.0 cm). Twenty-six were OATP1B1*15 noncarriers (homozygous for 521TT), the others were *15 carriers with at least one 521 T>C mutant allele. After single and multiple oral doses of 10 mg enalapril, plasma concentrations of enalapril in *15 noncarriers were lower than that in *15 carriers, with significant difference in area under the curve at steady state (AUC(ss)) between *15 noncarriers and *15 carriers (P = 0.048) in the multiple-dose phase. There were no significant differences in enalapril's AUC(0-24), C(max), or the ratio of the AUC(0-24h) in the single-dose study to the AUC(ss) (R(ac)) between the *15 carriers and noncarriers. In contrast to enalapril, the mean AUC(0-24h) and C(max) of enalaprilat in *15 noncarriers was significantly higher than those in *15 carriers (P = 0.040 and P = 0.027, respectively) in the single-dose phase. There were no significant differences in enalaprilat's AUC(ss) or C(maxss) between the 2 groups in the multiple-dose phase. For the 3 groups classified according to the effect of A388G variant in all subjects homozygous for 521T (TT), *1a/*1a, *1a/*1b, and *1b/*1b, no significant difference was found in AUC(0-24h), C(max), and T(max) of enalapril and enalaprilat.
In this small population of healthy Chinese men, the OATP1B1*15 allele and T521C variant appeared to be an important determinant of the pharmacokinetics of enalapril. There were significant differences between the *15 carriers and noncarriers in enalapril's AUC(ss) and enalaprilat's AUC(0-24h), C(max), and R(ac). However, there were no significant differences in enalapril's AUC(0-24), C(max), or enalaprilat's AUC(ss), C(maxss) between the *15 carriers and noncarriers. Enalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of the OATP1B1 gene may play a role in causing the interindividual pharmacokinetic differences of this drug. The purpose of this study was to investigate the functional significance of the OATP1B1 genetic polymorphism on the pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy Chinese adult male participants. This was a single-center, open-label, single- and multiple-dose study conducted in healthy Chinese male participants. Each participant received a single oral dose of 10 mg enalapril under fasting conditions, followed by enalapril 10 mg/d for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 24 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7; on day 7, samples were collected from 0 to 72 hours after drug administration. An HPLC-MS/MS method was used to determine plasma concentrations of enalapril and enalaprilat. A polymerase chain reaction technique was used for genotyping of 2 single nucleotide polymorphisms (SNPs) of the OATP1B1 gene: T521C and A388G. The pharmacokinetic parameters of enalapril and enalaprilat were then compared according to genotype groups, using 1-way ANOVA, except for Tmax in which the Mann-Whitney test or Kruskal-Wallis test was used. The study included 32 healthy Han Chinese male participants (age range, 18–28 years; weight range, 50.0–80.0 kg; height range,159–182.0 cm). Twenty-six were OATP1B1*15 noncarriers (homozygous for 521TT), the others were *15 carriers with at least one 521 T>C mutant allele. After single and multiple oral doses of 10 mg enalapril, plasma concentrations of enalapril in *15 noncarriers were lower than that in *15 carriers, with significant difference in area under the curve at steady state (AUCss) between *15 noncarriers and *15 carriers (P = 0.048) in the multiple-dose phase. There were no significant differences in enalapril's AUC0–24, Cmax, or the ratio of the AUC0–24h in the single-dose study to the AUCss (Rac) between the *15 carriers and noncarriers. In contrast to enalapril, the mean AUC0–24h and Cmax of enalaprilat in *15 noncarriers was significantly higher than those in *15 carriers (P = 0.040 and P = 0.027, respectively) in the single-dose phase. There were no significant differences in enalaprilat's AUCss or Cmaxss between the 2 groups in the multiple-dose phase. For the 3 groups classified according to the effect of A388G variant in all subjects homozygous for 521T (TT), *1a/*1a, *1a/*1b, and *1b/*1b, no significant difference was found in AUC0–24h, Cmax, and Tmax of enalapril and enalaprilat. In this small population of healthy Chinese men, the OATP1B1*15 allele and T521C variant appeared to be an important determinant of the pharmacokinetics of enalapril. There were significant differences between the *15 carriers and noncarriers in enalapril's AUCss and enalaprilat's AUC0–24h, Cmax, and Rac. However, there were no significant differences in enalapril's AUC0–24, Cmax, or enalaprilat's AUCss, Cmaxss between the *15 carriers and noncarriers. Enalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of the OATP1B1 gene may play a role in causing the interindividual pharmacokinetic differences of this drug. The purpose of this study was to investigate the functional significance of the OATP1B1 genetic polymorphism on the pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy Chinese adult male participants. This was a single-center, open-label, single- and multiple-dose study conducted in healthy Chinese male participants. Each participant received a single oral dose of 10 mg enalapril under fasting conditions, followed by enalapril 10 mg/d for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 24 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7; on day 7, samples were collected from 0 to 72 hours after drug administration. An HPLC-MS/MS method was used to determine plasma concentrations of enalapril and enalaprilat. A polymerase chain reaction technique was used for genotyping of 2 single nucleotide polymorphisms (SNPs) of the OATP1B1 gene: T521C and A388G. The pharmacokinetic parameters of enalapril and enalaprilat were then compared according to genotype groups, using 1-way ANOVA, except for Tmax in which the Mann-Whitney test or Kruskal-Wallis test was used. The study included 32 healthy Han Chinese male participants (age range, 18-28 years; weight range, 50.0-80.0 kg; height range,159-182.0 cm). Twenty-six were OATP1B1*15 noncarriers (homozygous for 521TT), the others were *15 carriers with at least one 521 T>C mutant allele. After single and multiple oral doses of 10 mg enalapril, plasma concentrations of enalapril in *15 noncarriers were lower than that in *15 carriers, with significant difference in area under the curve at steady state (AUCss) between *15 noncarriers and *15 carriers (P = 0.048) in the multiple-dose phase. There were no significant differences in enalapril's AUC0-24, Cmax, or the ratio of the AUC0-24h in the single-dose study to the AUCss (Rac) between the *15 carriers and noncarriers. In contrast to enalapril, the mean AUC0-24h and Cmax of enalaprilat in *15 noncarriers was significantly higher than those in *15 carriers (P = 0.040 and P = 0.027, respectively) in the single-dose phase. There were no significant differences in enalaprilat's AUCss or Cmaxss between the 2 groups in the multiple-dose phase. For the 3 groups classified according to the effect of A388G variant in all subjects homozygous for 521T (TT), *1a/*1a, *1a/*1b, and *1b/*1b, no significant difference was found in AUC0-24h, Cmax, and Tmax of enalapril and enalaprilat. In this small population of healthy Chinese men, the OATP1B1*15 allele and T521C variant appeared to be an important determinant of the pharmacokinetics of enalapril. There were significant differences between the *15 carriers and noncarriers in enalapril's AUCss and enalaprilat's AUC0-24h, Cmax, and Rac. However, there were no significant differences in enalapril's AUC0-24, Cmax, or enalaprilat's AUCss, Cmaxss between the *15 carriers and noncarriers. Abstract Background Enalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of the OATP1B1 gene may play a role in causing the interindividual pharmacokinetic differences of this drug. Objective The purpose of this study was to investigate the functional significance of the OATP1B1 genetic polymorphism on the pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy Chinese adult male participants. Methods This was a single-center, open-label, single- and multiple-dose study conducted in healthy Chinese male participants. Each participant received a single oral dose of 10 mg enalapril under fasting conditions, followed by enalapril 10 mg/d for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 24 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7; on day 7, samples were collected from 0 to 72 hours after drug administration. An HPLC-MS/MS method was used to determine plasma concentrations of enalapril and enalaprilat. A polymerase chain reaction technique was used for genotyping of 2 single nucleotide polymorphisms (SNPs) of the OATP1B1 gene: T521C and A388G. The pharmacokinetic parameters of enalapril and enalaprilat were then compared according to genotype groups, using 1-way ANOVA, except for Tmax in which the Mann-Whitney test or Kruskal-Wallis test was used. Results The study included 32 healthy Han Chinese male participants (age range, 18–28 years; weight range, 50.0–80.0 kg; height range,159–182.0 cm). Twenty-six were OATP1B1*15 noncarriers (homozygous for 521TT), the others were *15 carriers with at least one 521 T>C mutant allele. After single and multiple oral doses of 10 mg enalapril, plasma concentrations of enalapril in *15 noncarriers were lower than that in *15 carriers, with significant difference in area under the curve at steady state (AUCss ) between *15 noncarriers and *15 carriers ( P = 0.048) in the multiple-dose phase. There were no significant differences in enalapril's AUC0–24 , Cmax , or the ratio of the AUC0–24h in the single-dose study to the AUCss (Rac ) between the *15 carriers and noncarriers. In contrast to enalapril, the mean AUC0–24h and Cmax of enalaprilat in *15 noncarriers was significantly higher than those in *15 carriers ( P = 0.040 and P = 0.027, respectively) in the single-dose phase. There were no significant differences in enalaprilat's AUCss or Cmaxss between the 2 groups in the multiple-dose phase. For the 3 groups classified according to the effect of A388G variant in all subjects homozygous for 521T (TT), *1a/*1a, *1a/*1b, and *1b/*1b, no significant difference was found in AUC0–24h , Cmax , and Tmax of enalapril and enalaprilat. Conclusions In this small population of healthy Chinese men, the OATP1B1*15 allele and T521C variant appeared to be an important determinant of the pharmacokinetics of enalapril. There were significant differences between the *15 carriers and noncarriers in enalapril's AUCss and enalaprilat's AUC0–24h , Cmax , and Rac . However, there were no significant differences in enalapril's AUC0–24 , Cmax , or enalaprilat's AUCss , Cmaxss between the *15 carriers and noncarriers. Enalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of the OATP1B1 gene may play a role in causing the interindividual pharmacokinetic differences of this drug.BACKGROUNDEnalapril is an angiotensin-converting enzyme (ACE) inhibitor approved for the treatment of mild to severe hypertension and congestive heart failure. There is evidence that enalapril may be an organic anion-transporting polypeptide 1B1 (OATP1B1) substrate, suggesting that genetic polymorphisms of the OATP1B1 gene may play a role in causing the interindividual pharmacokinetic differences of this drug.The purpose of this study was to investigate the functional significance of the OATP1B1 genetic polymorphism on the pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy Chinese adult male participants.OBJECTIVEThe purpose of this study was to investigate the functional significance of the OATP1B1 genetic polymorphism on the pharmacokinetics of enalapril and its active metabolite enalaprilat in healthy Chinese adult male participants.This was a single-center, open-label, single- and multiple-dose study conducted in healthy Chinese male participants. Each participant received a single oral dose of 10 mg enalapril under fasting conditions, followed by enalapril 10 mg/d for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 24 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7; on day 7, samples were collected from 0 to 72 hours after drug administration. An HPLC-MS/MS method was used to determine plasma concentrations of enalapril and enalaprilat. A polymerase chain reaction technique was used for genotyping of 2 single nucleotide polymorphisms (SNPs) of the OATP1B1 gene: T521C and A388G. The pharmacokinetic parameters of enalapril and enalaprilat were then compared according to genotype groups, using 1-way ANOVA, except for T(max) in which the Mann-Whitney test or Kruskal-Wallis test was used.METHODSThis was a single-center, open-label, single- and multiple-dose study conducted in healthy Chinese male participants. Each participant received a single oral dose of 10 mg enalapril under fasting conditions, followed by enalapril 10 mg/d for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 24 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7; on day 7, samples were collected from 0 to 72 hours after drug administration. An HPLC-MS/MS method was used to determine plasma concentrations of enalapril and enalaprilat. A polymerase chain reaction technique was used for genotyping of 2 single nucleotide polymorphisms (SNPs) of the OATP1B1 gene: T521C and A388G. The pharmacokinetic parameters of enalapril and enalaprilat were then compared according to genotype groups, using 1-way ANOVA, except for T(max) in which the Mann-Whitney test or Kruskal-Wallis test was used.The study included 32 healthy Han Chinese male participants (age range, 18-28 years; weight range, 50.0-80.0 kg; height range,159-182.0 cm). Twenty-six were OATP1B1*15 noncarriers (homozygous for 521TT), the others were *15 carriers with at least one 521 T>C mutant allele. After single and multiple oral doses of 10 mg enalapril, plasma concentrations of enalapril in *15 noncarriers were lower than that in *15 carriers, with significant difference in area under the curve at steady state (AUC(ss)) between *15 noncarriers and *15 carriers (P = 0.048) in the multiple-dose phase. There were no significant differences in enalapril's AUC(0-24), C(max), or the ratio of the AUC(0-24h) in the single-dose study to the AUC(ss) (R(ac)) between the *15 carriers and noncarriers. In contrast to enalapril, the mean AUC(0-24h) and C(max) of enalaprilat in *15 noncarriers was significantly higher than those in *15 carriers (P = 0.040 and P = 0.027, respectively) in the single-dose phase. There were no significant differences in enalaprilat's AUC(ss) or C(maxss) between the 2 groups in the multiple-dose phase. For the 3 groups classified according to the effect of A388G variant in all subjects homozygous for 521T (TT), *1a/*1a, *1a/*1b, and *1b/*1b, no significant difference was found in AUC(0-24h), C(max), and T(max) of enalapril and enalaprilat.RESULTSThe study included 32 healthy Han Chinese male participants (age range, 18-28 years; weight range, 50.0-80.0 kg; height range,159-182.0 cm). Twenty-six were OATP1B1*15 noncarriers (homozygous for 521TT), the others were *15 carriers with at least one 521 T>C mutant allele. After single and multiple oral doses of 10 mg enalapril, plasma concentrations of enalapril in *15 noncarriers were lower than that in *15 carriers, with significant difference in area under the curve at steady state (AUC(ss)) between *15 noncarriers and *15 carriers (P = 0.048) in the multiple-dose phase. There were no significant differences in enalapril's AUC(0-24), C(max), or the ratio of the AUC(0-24h) in the single-dose study to the AUC(ss) (R(ac)) between the *15 carriers and noncarriers. In contrast to enalapril, the mean AUC(0-24h) and C(max) of enalaprilat in *15 noncarriers was significantly higher than those in *15 carriers (P = 0.040 and P = 0.027, respectively) in the single-dose phase. There were no significant differences in enalaprilat's AUC(ss) or C(maxss) between the 2 groups in the multiple-dose phase. For the 3 groups classified according to the effect of A388G variant in all subjects homozygous for 521T (TT), *1a/*1a, *1a/*1b, and *1b/*1b, no significant difference was found in AUC(0-24h), C(max), and T(max) of enalapril and enalaprilat.In this small population of healthy Chinese men, the OATP1B1*15 allele and T521C variant appeared to be an important determinant of the pharmacokinetics of enalapril. There were significant differences between the *15 carriers and noncarriers in enalapril's AUC(ss) and enalaprilat's AUC(0-24h), C(max), and R(ac). However, there were no significant differences in enalapril's AUC(0-24), C(max), or enalaprilat's AUC(ss), C(maxss) between the *15 carriers and noncarriers.CONCLUSIONSIn this small population of healthy Chinese men, the OATP1B1*15 allele and T521C variant appeared to be an important determinant of the pharmacokinetics of enalapril. There were significant differences between the *15 carriers and noncarriers in enalapril's AUC(ss) and enalaprilat's AUC(0-24h), C(max), and R(ac). However, there were no significant differences in enalapril's AUC(0-24), C(max), or enalaprilat's AUC(ss), C(maxss) between the *15 carriers and noncarriers. |
| Author | Han, Lulu Li, Yishi Tian, Lei Xie, Shuang Jiang, Juanjuan Huang, Yiling Liu, Hong |
| Author_xml | – sequence: 1 givenname: Lei surname: Tian fullname: Tian, Lei – sequence: 2 givenname: Hong surname: Liu fullname: Liu, Hong – sequence: 3 givenname: Shuang surname: Xie fullname: Xie, Shuang – sequence: 4 givenname: Juanjuan surname: Jiang fullname: Jiang, Juanjuan – sequence: 5 givenname: Lulu surname: Han fullname: Han, Lulu – sequence: 6 givenname: Yiling surname: Huang fullname: Huang, Yiling – sequence: 7 givenname: Yishi surname: Li fullname: Li, Yishi email: LiYiShi@public3.bta.net.cn |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24327250$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21665049$$D View this record in MEDLINE/PubMed |
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| DOI | 10.1016/j.clinthera.2011.04.018 |
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| Keywords | pharmacokinetics OATP1B1 polymorphism enalaprilat enalapril Human Genetic variability Healthy subject Enzyme Single dose Enzyme inhibitor Genotype Multiple dose Peptidases Organic anion Enalapril Peptidyl-dipeptidase A Polypeptide Enalaprilat Hydrolases Peptidyl-dipeptidases Antihypertensive agent Chinese Pharmacokinetics ACE inhibitor Polymorphism |
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Temocaprilat, a novel angiotensin converting enzyme inhibitor, is excreted in bile via an ATP dependent active transporter (cMOAT) that is deficient in Eisai hyperbilirubinemic mutant rats (EHBR) publication-title: J Pharmacol Exp Ther doi: 10.1016/S0022-3565(24)36523-1 |
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| Title | Effect of Organic Anion-Transporting Polypeptide 1B1 (OATP1B1) Polymorphism on the Single- and Multiple-Dose Pharmacokinetics of Enalapril in Healthy Chinese Adult Men |
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