Omeprazole limited sampling strategies to predict area under the concentration–time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping
Purpose To develop a limited sampling strategy (LSS) to predict area under the concentration–time curve (AUC) ratios of omeprazole (AUC OPZ ) to its metabolites 5-hydroxyomeprazole (AUC 5OH ) and omeprazole sulfone (AUC SUL ) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. Methods D...
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| Veröffentlicht in: | European journal of clinical pharmacology 2012-04, Vol.68 (4), p.407-413 |
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| creator | Lawson, Eileen B. Wu, Jerry C. Baldwin, R. Michael Ingelman-Sundberg, Magnus Rosenborg, Staffan Yim, Dong-Seok Yin, Ophelia Q. P. Capparelli, Edmund V. Ma, Joseph D. |
| description | Purpose
To develop a limited sampling strategy (LSS) to predict area under the concentration–time curve (AUC) ratios of omeprazole (AUC
OPZ
) to its metabolites 5-hydroxyomeprazole (AUC
5OH
) and omeprazole sulfone (AUC
SUL
) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A.
Methods
Data were obtained from 37 (4 women) Caucasian, Chinese, and Korean healthy adults from three published studies. The AUC
OPZ
, AUC
5OH
, and AUC
SUL
were calculated via noncompartmental analysis. Observed AUC
OPZ, OBS
/AUC
5OH, OBS
and AUC
OPZ, OBS
/AUC
SUL, OBS
were determined. Plasma concentrations of omeprazole, 5-hydroxyomeprazole, and omeprazole sulfone at 1, 1.5, 2, 3, 4, 6, and 8 h post-dose were used to generate limited sampling strategy (LSS) models to predict AUC
OPZ,PRE
/AUC
5OH,PRE
and AUC
OPZ,PRE/
AUC
SUL,PRE
. Bias and precision were assessed via percentage mean prediction error (%MPE) and percentage mean absolute error (%MAE), with acceptable limits being |
| doi_str_mv | 10.1007/s00228-011-1136-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_541274</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2608765101</sourcerecordid><originalsourceid>FETCH-LOGICAL-c488t-1f9a00347321b7344a80638296a9e32542a4ebdfe1f0d0fff61ed882c50be2503</originalsourceid><addsrcrecordid>eNp1kU2O1DAQhSMEYpqBA7BBFhLLQJXt_LEbtfiTRhoWsLYcp9LtIYmD7YCaFXdgy-k4Ce7pnunVrGxVfa_qlV6WPUd4jQDVmwDAeZ0DYo4oynz3IFuhFDxHkPgwWwEIzMumgrPsSQjXAFg0IB5nZ5wDNNjAKvt7NdLs9S83EBvsaCN1LOhxHuy0YSF6HWljKbDo2OypsyYy7UmzZerIs7glZtxkaNqT1k3_fv-JdkzFxf8gdlMLb5ndzzM3QGC988zsojNb7xL5WRbA-BobpqeOiQs2b2lycTcnA0-zR70eAj07vufZ1_fvvqw_5pdXHz6tLy5zI-s65tg3Op0qK8GxrYSUuoZS1LwpdUOCF5JrSW3XE_bQQd_3JVJX19wU0BIvQJxn-WFu-Enz0qrZ21H7nXLaqmPpW_qRKiTySia-uZefvetOolshcsnLqpB77cuDNoHfFwpRXbvFT-k81fCqLgBFkSA8QMa7EDz1dysQ1D56dYhepejVPnq1S5oXx8FLO1J3p7jNOgGvjoAORg-915Ox4cQVpayTg8Tx43WpNW3Inxzev_0_LUvKpQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>927850135</pqid></control><display><type>article</type><title>Omeprazole limited sampling strategies to predict area under the concentration–time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Lawson, Eileen B. ; Wu, Jerry C. ; Baldwin, R. Michael ; Ingelman-Sundberg, Magnus ; Rosenborg, Staffan ; Yim, Dong-Seok ; Yin, Ophelia Q. P. ; Capparelli, Edmund V. ; Ma, Joseph D.</creator><creatorcontrib>Lawson, Eileen B. ; Wu, Jerry C. ; Baldwin, R. Michael ; Ingelman-Sundberg, Magnus ; Rosenborg, Staffan ; Yim, Dong-Seok ; Yin, Ophelia Q. P. ; Capparelli, Edmund V. ; Ma, Joseph D.</creatorcontrib><description>Purpose
To develop a limited sampling strategy (LSS) to predict area under the concentration–time curve (AUC) ratios of omeprazole (AUC
OPZ
) to its metabolites 5-hydroxyomeprazole (AUC
5OH
) and omeprazole sulfone (AUC
SUL
) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A.
Methods
Data were obtained from 37 (4 women) Caucasian, Chinese, and Korean healthy adults from three published studies. The AUC
OPZ
, AUC
5OH
, and AUC
SUL
were calculated via noncompartmental analysis. Observed AUC
OPZ, OBS
/AUC
5OH, OBS
and AUC
OPZ, OBS
/AUC
SUL, OBS
were determined. Plasma concentrations of omeprazole, 5-hydroxyomeprazole, and omeprazole sulfone at 1, 1.5, 2, 3, 4, 6, and 8 h post-dose were used to generate limited sampling strategy (LSS) models to predict AUC
OPZ,PRE
/AUC
5OH,PRE
and AUC
OPZ,PRE/
AUC
SUL,PRE
. Bias and precision were assessed via percentage mean prediction error (%MPE) and percentage mean absolute error (%MAE), with acceptable limits being <15%.
Results
For
CYP2C19
, the AUC
OPZ,OBS
/AUC
5OH,OBS
was [mean ± standard deviation (SD)] 2.10 ± 1.63. Five LSS models of AUC
OPZ,PRE
/AUC
5OH,PRE
were generated, but none met the bias or precision criteria. Upon stratification by
CYP2C19
genotype and ethnicity, a three-timepoint (at 1, 2, and 4 h) LSS model accurately predicted AUC
OPZ
/AUC
5OH
in Caucasian
CYP2C19*1/*1
subjects. For
CYP3A
, AUC
OPZ,OBS
/AUC
SUL,OBS
(mean ± SD) was 1.79 ± 0.67. All LSS models had unacceptable %MAE, even when stratified by
CYP2C19
genotype and ethnicity.
Conclusions
A LSS model to predict AUC
OPZ
/AUC
5OH
, and thus
CYP2C19
activity, was generated for Caucasian
CYP2C19*1/*1
subjects. However, additional model validation is needed prior to general use. LSS models to predict AUC
OPZ
/AUC
SUL
, and thus
CYP3A
activity, were not possible, even upon stratification by
CYP2C19
genotype and ethnicity.</description><identifier>ISSN: 0031-6970</identifier><identifier>ISSN: 1432-1041</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-011-1136-y</identifier><identifier>PMID: 22009190</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>2-Pyridinylmethylsulfinylbenzimidazoles - blood ; Adolescent ; Adult ; Anti-Ulcer Agents - blood ; Anti-Ulcer Agents - pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases - genetics ; Aryl Hydrocarbon Hydroxylases - metabolism ; Asian Continental Ancestry Group - genetics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP3A - metabolism ; Ethnicity ; European Continental Ancestry Group - genetics ; Female ; Genotype ; Genotype & phenotype ; Humans ; Male ; Medical sciences ; Medicin och hälsovetenskap ; Models, Biological ; Omeprazole - analogs & derivatives ; Omeprazole - blood ; Omeprazole - pharmacokinetics ; Pharmacokinetics and Disposition ; Pharmacology ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Phenotype ; Prescription drugs ; Side effects ; Young Adult</subject><ispartof>European journal of clinical pharmacology, 2012-04, Vol.68 (4), p.407-413</ispartof><rights>Springer-Verlag 2011</rights><rights>2015 INIST-CNRS</rights><rights>Springer-Verlag 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-1f9a00347321b7344a80638296a9e32542a4ebdfe1f0d0fff61ed882c50be2503</citedby><cites>FETCH-LOGICAL-c488t-1f9a00347321b7344a80638296a9e32542a4ebdfe1f0d0fff61ed882c50be2503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00228-011-1136-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00228-011-1136-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25648278$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22009190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:124267544$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Lawson, Eileen B.</creatorcontrib><creatorcontrib>Wu, Jerry C.</creatorcontrib><creatorcontrib>Baldwin, R. Michael</creatorcontrib><creatorcontrib>Ingelman-Sundberg, Magnus</creatorcontrib><creatorcontrib>Rosenborg, Staffan</creatorcontrib><creatorcontrib>Yim, Dong-Seok</creatorcontrib><creatorcontrib>Yin, Ophelia Q. P.</creatorcontrib><creatorcontrib>Capparelli, Edmund V.</creatorcontrib><creatorcontrib>Ma, Joseph D.</creatorcontrib><title>Omeprazole limited sampling strategies to predict area under the concentration–time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><addtitle>Eur J Clin Pharmacol</addtitle><description>Purpose
To develop a limited sampling strategy (LSS) to predict area under the concentration–time curve (AUC) ratios of omeprazole (AUC
OPZ
) to its metabolites 5-hydroxyomeprazole (AUC
5OH
) and omeprazole sulfone (AUC
SUL
) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A.
Methods
Data were obtained from 37 (4 women) Caucasian, Chinese, and Korean healthy adults from three published studies. The AUC
OPZ
, AUC
5OH
, and AUC
SUL
were calculated via noncompartmental analysis. Observed AUC
OPZ, OBS
/AUC
5OH, OBS
and AUC
OPZ, OBS
/AUC
SUL, OBS
were determined. Plasma concentrations of omeprazole, 5-hydroxyomeprazole, and omeprazole sulfone at 1, 1.5, 2, 3, 4, 6, and 8 h post-dose were used to generate limited sampling strategy (LSS) models to predict AUC
OPZ,PRE
/AUC
5OH,PRE
and AUC
OPZ,PRE/
AUC
SUL,PRE
. Bias and precision were assessed via percentage mean prediction error (%MPE) and percentage mean absolute error (%MAE), with acceptable limits being <15%.
Results
For
CYP2C19
, the AUC
OPZ,OBS
/AUC
5OH,OBS
was [mean ± standard deviation (SD)] 2.10 ± 1.63. Five LSS models of AUC
OPZ,PRE
/AUC
5OH,PRE
were generated, but none met the bias or precision criteria. Upon stratification by
CYP2C19
genotype and ethnicity, a three-timepoint (at 1, 2, and 4 h) LSS model accurately predicted AUC
OPZ
/AUC
5OH
in Caucasian
CYP2C19*1/*1
subjects. For
CYP3A
, AUC
OPZ,OBS
/AUC
SUL,OBS
(mean ± SD) was 1.79 ± 0.67. All LSS models had unacceptable %MAE, even when stratified by
CYP2C19
genotype and ethnicity.
Conclusions
A LSS model to predict AUC
OPZ
/AUC
5OH
, and thus
CYP2C19
activity, was generated for Caucasian
CYP2C19*1/*1
subjects. However, additional model validation is needed prior to general use. LSS models to predict AUC
OPZ
/AUC
SUL
, and thus
CYP3A
activity, were not possible, even upon stratification by
CYP2C19
genotype and ethnicity.</description><subject>2-Pyridinylmethylsulfinylbenzimidazoles - blood</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Anti-Ulcer Agents - blood</subject><subject>Anti-Ulcer Agents - pharmacokinetics</subject><subject>Area Under Curve</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Aryl Hydrocarbon Hydroxylases - metabolism</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cytochrome P-450 CYP2C19</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>Ethnicity</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Models, Biological</subject><subject>Omeprazole - analogs & derivatives</subject><subject>Omeprazole - blood</subject><subject>Omeprazole - pharmacokinetics</subject><subject>Pharmacokinetics and Disposition</subject><subject>Pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Phenotype</subject><subject>Prescription drugs</subject><subject>Side effects</subject><subject>Young Adult</subject><issn>0031-6970</issn><issn>1432-1041</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kU2O1DAQhSMEYpqBA7BBFhLLQJXt_LEbtfiTRhoWsLYcp9LtIYmD7YCaFXdgy-k4Ce7pnunVrGxVfa_qlV6WPUd4jQDVmwDAeZ0DYo4oynz3IFuhFDxHkPgwWwEIzMumgrPsSQjXAFg0IB5nZ5wDNNjAKvt7NdLs9S83EBvsaCN1LOhxHuy0YSF6HWljKbDo2OypsyYy7UmzZerIs7glZtxkaNqT1k3_fv-JdkzFxf8gdlMLb5ndzzM3QGC988zsojNb7xL5WRbA-BobpqeOiQs2b2lycTcnA0-zR70eAj07vufZ1_fvvqw_5pdXHz6tLy5zI-s65tg3Op0qK8GxrYSUuoZS1LwpdUOCF5JrSW3XE_bQQd_3JVJX19wU0BIvQJxn-WFu-Enz0qrZ21H7nXLaqmPpW_qRKiTySia-uZefvetOolshcsnLqpB77cuDNoHfFwpRXbvFT-k81fCqLgBFkSA8QMa7EDz1dysQ1D56dYhepejVPnq1S5oXx8FLO1J3p7jNOgGvjoAORg-915Ox4cQVpayTg8Tx43WpNW3Inxzev_0_LUvKpQ</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Lawson, Eileen B.</creator><creator>Wu, Jerry C.</creator><creator>Baldwin, R. Michael</creator><creator>Ingelman-Sundberg, Magnus</creator><creator>Rosenborg, Staffan</creator><creator>Yim, Dong-Seok</creator><creator>Yin, Ophelia Q. P.</creator><creator>Capparelli, Edmund V.</creator><creator>Ma, Joseph D.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20120401</creationdate><title>Omeprazole limited sampling strategies to predict area under the concentration–time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping</title><author>Lawson, Eileen B. ; Wu, Jerry C. ; Baldwin, R. Michael ; Ingelman-Sundberg, Magnus ; Rosenborg, Staffan ; Yim, Dong-Seok ; Yin, Ophelia Q. P. ; Capparelli, Edmund V. ; Ma, Joseph D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-1f9a00347321b7344a80638296a9e32542a4ebdfe1f0d0fff61ed882c50be2503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>2-Pyridinylmethylsulfinylbenzimidazoles - blood</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Anti-Ulcer Agents - blood</topic><topic>Anti-Ulcer Agents - pharmacokinetics</topic><topic>Area Under Curve</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Aryl Hydrocarbon Hydroxylases - metabolism</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cytochrome P-450 CYP2C19</topic><topic>Cytochrome P-450 CYP3A - metabolism</topic><topic>Ethnicity</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Female</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Models, Biological</topic><topic>Omeprazole - analogs & derivatives</topic><topic>Omeprazole - blood</topic><topic>Omeprazole - pharmacokinetics</topic><topic>Pharmacokinetics and Disposition</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Phenotype</topic><topic>Prescription drugs</topic><topic>Side effects</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lawson, Eileen B.</creatorcontrib><creatorcontrib>Wu, Jerry C.</creatorcontrib><creatorcontrib>Baldwin, R. Michael</creatorcontrib><creatorcontrib>Ingelman-Sundberg, Magnus</creatorcontrib><creatorcontrib>Rosenborg, Staffan</creatorcontrib><creatorcontrib>Yim, Dong-Seok</creatorcontrib><creatorcontrib>Yin, Ophelia Q. P.</creatorcontrib><creatorcontrib>Capparelli, Edmund V.</creatorcontrib><creatorcontrib>Ma, Joseph D.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lawson, Eileen B.</au><au>Wu, Jerry C.</au><au>Baldwin, R. Michael</au><au>Ingelman-Sundberg, Magnus</au><au>Rosenborg, Staffan</au><au>Yim, Dong-Seok</au><au>Yin, Ophelia Q. P.</au><au>Capparelli, Edmund V.</au><au>Ma, Joseph D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Omeprazole limited sampling strategies to predict area under the concentration–time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping</atitle><jtitle>European journal of clinical pharmacology</jtitle><stitle>Eur J Clin Pharmacol</stitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>68</volume><issue>4</issue><spage>407</spage><epage>413</epage><pages>407-413</pages><issn>0031-6970</issn><issn>1432-1041</issn><eissn>1432-1041</eissn><abstract>Purpose
To develop a limited sampling strategy (LSS) to predict area under the concentration–time curve (AUC) ratios of omeprazole (AUC
OPZ
) to its metabolites 5-hydroxyomeprazole (AUC
5OH
) and omeprazole sulfone (AUC
SUL
) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A.
Methods
Data were obtained from 37 (4 women) Caucasian, Chinese, and Korean healthy adults from three published studies. The AUC
OPZ
, AUC
5OH
, and AUC
SUL
were calculated via noncompartmental analysis. Observed AUC
OPZ, OBS
/AUC
5OH, OBS
and AUC
OPZ, OBS
/AUC
SUL, OBS
were determined. Plasma concentrations of omeprazole, 5-hydroxyomeprazole, and omeprazole sulfone at 1, 1.5, 2, 3, 4, 6, and 8 h post-dose were used to generate limited sampling strategy (LSS) models to predict AUC
OPZ,PRE
/AUC
5OH,PRE
and AUC
OPZ,PRE/
AUC
SUL,PRE
. Bias and precision were assessed via percentage mean prediction error (%MPE) and percentage mean absolute error (%MAE), with acceptable limits being <15%.
Results
For
CYP2C19
, the AUC
OPZ,OBS
/AUC
5OH,OBS
was [mean ± standard deviation (SD)] 2.10 ± 1.63. Five LSS models of AUC
OPZ,PRE
/AUC
5OH,PRE
were generated, but none met the bias or precision criteria. Upon stratification by
CYP2C19
genotype and ethnicity, a three-timepoint (at 1, 2, and 4 h) LSS model accurately predicted AUC
OPZ
/AUC
5OH
in Caucasian
CYP2C19*1/*1
subjects. For
CYP3A
, AUC
OPZ,OBS
/AUC
SUL,OBS
(mean ± SD) was 1.79 ± 0.67. All LSS models had unacceptable %MAE, even when stratified by
CYP2C19
genotype and ethnicity.
Conclusions
A LSS model to predict AUC
OPZ
/AUC
5OH
, and thus
CYP2C19
activity, was generated for Caucasian
CYP2C19*1/*1
subjects. However, additional model validation is needed prior to general use. LSS models to predict AUC
OPZ
/AUC
SUL
, and thus
CYP3A
activity, were not possible, even upon stratification by
CYP2C19
genotype and ethnicity.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22009190</pmid><doi>10.1007/s00228-011-1136-y</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-6970 |
| ispartof | European journal of clinical pharmacology, 2012-04, Vol.68 (4), p.407-413 |
| issn | 0031-6970 1432-1041 1432-1041 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_541274 |
| source | MEDLINE; SpringerNature Journals |
| subjects | 2-Pyridinylmethylsulfinylbenzimidazoles - blood Adolescent Adult Anti-Ulcer Agents - blood Anti-Ulcer Agents - pharmacokinetics Area Under Curve Aryl Hydrocarbon Hydroxylases - genetics Aryl Hydrocarbon Hydroxylases - metabolism Asian Continental Ancestry Group - genetics Biological and medical sciences Biomedical and Life Sciences Biomedicine Cytochrome P-450 CYP2C19 Cytochrome P-450 CYP3A - metabolism Ethnicity European Continental Ancestry Group - genetics Female Genotype Genotype & phenotype Humans Male Medical sciences Medicin och hälsovetenskap Models, Biological Omeprazole - analogs & derivatives Omeprazole - blood Omeprazole - pharmacokinetics Pharmacokinetics and Disposition Pharmacology Pharmacology. Drug treatments Pharmacology/Toxicology Phenotype Prescription drugs Side effects Young Adult |
| title | Omeprazole limited sampling strategies to predict area under the concentration–time curve ratios: implications for cytochrome P450 2C19 and 3A phenotyping |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T04%3A58%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Omeprazole%20limited%20sampling%20strategies%20to%20predict%20area%20under%20the%20concentration%E2%80%93time%20curve%20ratios:%20implications%20for%20cytochrome%20P450%202C19%20and%203A%20phenotyping&rft.jtitle=European%20journal%20of%20clinical%20pharmacology&rft.au=Lawson,%20Eileen%20B.&rft.date=2012-04-01&rft.volume=68&rft.issue=4&rft.spage=407&rft.epage=413&rft.pages=407-413&rft.issn=0031-6970&rft.eissn=1432-1041&rft_id=info:doi/10.1007/s00228-011-1136-y&rft_dat=%3Cproquest_swepu%3E2608765101%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=927850135&rft_id=info:pmid/22009190&rfr_iscdi=true |