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Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients—implications for therapeutic drug monitoring
Purpose To evaluate the relationship between total and free MPA pharmacokinetic (PK) parameters and renal outcome markers, and to verify whether conducting therapeutic drug monitoring (TDM) in lupus nephritis (LN) patients would be of value in routine clinical practice. Methods Eighty-four samples w...
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| Published in: | European journal of clinical pharmacology 2019-03, Vol.75 (3), p.371-379 |
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| container_end_page | 379 |
| container_issue | 3 |
| container_start_page | 371 |
| container_title | European journal of clinical pharmacology |
| container_volume | 75 |
| creator | Łuszczyńska, Paulina Pawiński, Tomasz Kunicki, Paweł K. Durlik, Magdalena Augustyniak-Bartosik, Hanna Hurkacz, Magdalena |
| description | Purpose
To evaluate the relationship between total and free MPA pharmacokinetic (PK) parameters and renal outcome markers, and to verify whether conducting therapeutic drug monitoring (TDM) in lupus nephritis (LN) patients would be of value in routine clinical practice.
Methods
Eighty-four samples were collected from sixteen LN patients. Total and free MPA concentrations were measured at predose, 0.5 and 2 h after mycophenolate mofetil (MMF) intake. Area under the concentration time curve from 0 to 2 h (AUC
0–2
) and free fraction were calculated.
Results
High between-patient variability was observed (CV% of 53.5% for dose-normalized total MPA AUC
0–2
). A significant but weak correlation between dose-normalized total C
0
and AUC
0–2
was noted (
r
= 0.5699). Dose-normalized total C
0
above 2.76 μg/mL·g may indicate patients with eGFR |
| doi_str_mv | 10.1007/s00228-018-2599-x |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2133074147</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2133074147</sourcerecordid><originalsourceid>FETCH-LOGICAL-c330x-dccbff9073fe165dfa8aa2c95023658b247df773b100ec9b269ee03da52936fc3</originalsourceid><addsrcrecordid>eNp1kMtqHDEQRUVwiMdOPiAbI_C67ZLUj9EymPgBhmThrIVaD4_sbkmR1DDeZeM_8Bf6S6JhnGSVVVFw6l7qIPSZwBkBGM4zAKXrBsi6oR3nzfYdWpGW0YZASw7QCoCRpucDHKKjnB8ASMeBfUCHDFoGlLQr9Px9I9MsVXh03hSnMg4W22QMll7jEoqc8PykQtwYHyansFROY-ex1MtU8LTEJWNv4ia54jKOsjjjS3799eLmWPm6B5-xDQmXjUkymqW2YJ2WezwH70pIzt9_RO-tnLL59DaP0Y_Lr3cX183tt6ubiy-3jWIMto1WarSWw8CsIX2nrVxLSRXvgLK-W4-0HbQdBjZWO0bxkfbcGGBadpSz3ip2jE73uTGFn4vJRTyEJflaKSipFUNL2qFSZE-pFHJOxoqY3CzTkyAgduLFXryo4sVOvNjWm5O35GWcjf578cd0BegeyHH3sUn_qv-f-hvUSJNT</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2133074147</pqid></control><display><type>article</type><title>Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients—implications for therapeutic drug monitoring</title><source>Springer Nature</source><creator>Łuszczyńska, Paulina ; Pawiński, Tomasz ; Kunicki, Paweł K. ; Durlik, Magdalena ; Augustyniak-Bartosik, Hanna ; Hurkacz, Magdalena</creator><creatorcontrib>Łuszczyńska, Paulina ; Pawiński, Tomasz ; Kunicki, Paweł K. ; Durlik, Magdalena ; Augustyniak-Bartosik, Hanna ; Hurkacz, Magdalena</creatorcontrib><description>Purpose
To evaluate the relationship between total and free MPA pharmacokinetic (PK) parameters and renal outcome markers, and to verify whether conducting therapeutic drug monitoring (TDM) in lupus nephritis (LN) patients would be of value in routine clinical practice.
Methods
Eighty-four samples were collected from sixteen LN patients. Total and free MPA concentrations were measured at predose, 0.5 and 2 h after mycophenolate mofetil (MMF) intake. Area under the concentration time curve from 0 to 2 h (AUC
0–2
) and free fraction were calculated.
Results
High between-patient variability was observed (CV% of 53.5% for dose-normalized total MPA AUC
0–2
). A significant but weak correlation between dose-normalized total C
0
and AUC
0–2
was noted (
r
= 0.5699). Dose-normalized total C
0
above 2.76 μg/mL·g may indicate patients with eGFR < 81 mL/min with sensitivity of 83.3% and specificity of 75.0%. Hypoalbuminemic LN patients demonstrated significantly elevated MPA free fraction when compared with patients with serum albumin concentration ≥ 3.5 g/dL (1.49 ± 0.64% vs 1.08 ± 0.75%).
Conclusion
This study examined relationship between free and total pharmacokinetic MPA parameters as well as the effect of hypoalbuminemia on MPA plasma protein binding in adult LN patients. The study results suggest that TDM of MPA in LN seems to be a more reasonable approach than the fixed-dose protocol. Moreover, predose total MPA concentration may be a possible estimation of MPA exposure, while monitoring free rather than total MPA may be more beneficial in hypoalbuminemic patients.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-018-2599-x</identifier><identifier>PMID: 30430214</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Area Under Curve ; Autoimmune diseases ; Biomedical and Life Sciences ; Biomedicine ; Concentration time ; Dose-Response Relationship, Drug ; Drug dosages ; Drug Monitoring ; Epidermal growth factor receptors ; Female ; Humans ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - therapeutic use ; Kidney - drug effects ; Kidney - metabolism ; Kidney Function Tests ; Lupus ; Lupus nephritis ; Lupus Nephritis - blood ; Lupus Nephritis - drug therapy ; Male ; Mycophenolate mofetil ; Mycophenolic acid ; Mycophenolic Acid - administration & dosage ; Mycophenolic Acid - blood ; Mycophenolic Acid - therapeutic use ; Nephritis ; Pharmacokinetics ; Pharmacokinetics and Disposition ; Pharmacology/Toxicology ; Therapeutic drug monitoring</subject><ispartof>European journal of clinical pharmacology, 2019-03, Vol.75 (3), p.371-379</ispartof><rights>The Author(s) 2018</rights><rights>European Journal of Clinical Pharmacology is a copyright of Springer, (2018). All Rights Reserved. © 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c330x-dccbff9073fe165dfa8aa2c95023658b247df773b100ec9b269ee03da52936fc3</citedby><cites>FETCH-LOGICAL-c330x-dccbff9073fe165dfa8aa2c95023658b247df773b100ec9b269ee03da52936fc3</cites><orcidid>0000-0003-4622-8935</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30430214$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Łuszczyńska, Paulina</creatorcontrib><creatorcontrib>Pawiński, Tomasz</creatorcontrib><creatorcontrib>Kunicki, Paweł K.</creatorcontrib><creatorcontrib>Durlik, Magdalena</creatorcontrib><creatorcontrib>Augustyniak-Bartosik, Hanna</creatorcontrib><creatorcontrib>Hurkacz, Magdalena</creatorcontrib><title>Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients—implications for therapeutic drug monitoring</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><addtitle>Eur J Clin Pharmacol</addtitle><description>Purpose
To evaluate the relationship between total and free MPA pharmacokinetic (PK) parameters and renal outcome markers, and to verify whether conducting therapeutic drug monitoring (TDM) in lupus nephritis (LN) patients would be of value in routine clinical practice.
Methods
Eighty-four samples were collected from sixteen LN patients. Total and free MPA concentrations were measured at predose, 0.5 and 2 h after mycophenolate mofetil (MMF) intake. Area under the concentration time curve from 0 to 2 h (AUC
0–2
) and free fraction were calculated.
Results
High between-patient variability was observed (CV% of 53.5% for dose-normalized total MPA AUC
0–2
). A significant but weak correlation between dose-normalized total C
0
and AUC
0–2
was noted (
r
= 0.5699). Dose-normalized total C
0
above 2.76 μg/mL·g may indicate patients with eGFR < 81 mL/min with sensitivity of 83.3% and specificity of 75.0%. Hypoalbuminemic LN patients demonstrated significantly elevated MPA free fraction when compared with patients with serum albumin concentration ≥ 3.5 g/dL (1.49 ± 0.64% vs 1.08 ± 0.75%).
Conclusion
This study examined relationship between free and total pharmacokinetic MPA parameters as well as the effect of hypoalbuminemia on MPA plasma protein binding in adult LN patients. The study results suggest that TDM of MPA in LN seems to be a more reasonable approach than the fixed-dose protocol. Moreover, predose total MPA concentration may be a possible estimation of MPA exposure, while monitoring free rather than total MPA may be more beneficial in hypoalbuminemic patients.</description><subject>Adult</subject><subject>Area Under Curve</subject><subject>Autoimmune diseases</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Concentration time</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug dosages</subject><subject>Drug Monitoring</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Humans</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney Function Tests</subject><subject>Lupus</subject><subject>Lupus nephritis</subject><subject>Lupus Nephritis - blood</subject><subject>Lupus Nephritis - drug therapy</subject><subject>Male</subject><subject>Mycophenolate mofetil</subject><subject>Mycophenolic acid</subject><subject>Mycophenolic Acid - administration & dosage</subject><subject>Mycophenolic Acid - blood</subject><subject>Mycophenolic Acid - therapeutic use</subject><subject>Nephritis</subject><subject>Pharmacokinetics</subject><subject>Pharmacokinetics and Disposition</subject><subject>Pharmacology/Toxicology</subject><subject>Therapeutic drug monitoring</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kMtqHDEQRUVwiMdOPiAbI_C67ZLUj9EymPgBhmThrIVaD4_sbkmR1DDeZeM_8Bf6S6JhnGSVVVFw6l7qIPSZwBkBGM4zAKXrBsi6oR3nzfYdWpGW0YZASw7QCoCRpucDHKKjnB8ASMeBfUCHDFoGlLQr9Px9I9MsVXh03hSnMg4W22QMll7jEoqc8PykQtwYHyansFROY-ex1MtU8LTEJWNv4ia54jKOsjjjS3799eLmWPm6B5-xDQmXjUkymqW2YJ2WezwH70pIzt9_RO-tnLL59DaP0Y_Lr3cX183tt6ubiy-3jWIMto1WarSWw8CsIX2nrVxLSRXvgLK-W4-0HbQdBjZWO0bxkfbcGGBadpSz3ip2jE73uTGFn4vJRTyEJflaKSipFUNL2qFSZE-pFHJOxoqY3CzTkyAgduLFXryo4sVOvNjWm5O35GWcjf578cd0BegeyHH3sUn_qv-f-hvUSJNT</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Łuszczyńska, Paulina</creator><creator>Pawiński, Tomasz</creator><creator>Kunicki, Paweł K.</creator><creator>Durlik, Magdalena</creator><creator>Augustyniak-Bartosik, Hanna</creator><creator>Hurkacz, Magdalena</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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><orcidid>https://orcid.org/0000-0003-4622-8935</orcidid></search><sort><creationdate>201903</creationdate><title>Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients—implications for therapeutic drug monitoring</title><author>Łuszczyńska, Paulina ; Pawiński, Tomasz ; Kunicki, Paweł K. ; Durlik, Magdalena ; Augustyniak-Bartosik, Hanna ; Hurkacz, Magdalena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330x-dccbff9073fe165dfa8aa2c95023658b247df773b100ec9b269ee03da52936fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Area Under Curve</topic><topic>Autoimmune diseases</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Concentration time</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug dosages</topic><topic>Drug Monitoring</topic><topic>Epidermal growth factor receptors</topic><topic>Female</topic><topic>Humans</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney Function Tests</topic><topic>Lupus</topic><topic>Lupus nephritis</topic><topic>Lupus Nephritis - blood</topic><topic>Lupus Nephritis - drug therapy</topic><topic>Male</topic><topic>Mycophenolate mofetil</topic><topic>Mycophenolic acid</topic><topic>Mycophenolic Acid - administration & dosage</topic><topic>Mycophenolic Acid - blood</topic><topic>Mycophenolic Acid - therapeutic use</topic><topic>Nephritis</topic><topic>Pharmacokinetics</topic><topic>Pharmacokinetics and Disposition</topic><topic>Pharmacology/Toxicology</topic><topic>Therapeutic drug monitoring</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Łuszczyńska, Paulina</creatorcontrib><creatorcontrib>Pawiński, Tomasz</creatorcontrib><creatorcontrib>Kunicki, Paweł K.</creatorcontrib><creatorcontrib>Durlik, Magdalena</creatorcontrib><creatorcontrib>Augustyniak-Bartosik, Hanna</creatorcontrib><creatorcontrib>Hurkacz, Magdalena</creatorcontrib><collection>Springer Open Access</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>ProQuest Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest 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)</collection><collection>ProQuest Central</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>PML(ProQuest Medical Library)</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><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Łuszczyńska, Paulina</au><au>Pawiński, Tomasz</au><au>Kunicki, Paweł K.</au><au>Durlik, Magdalena</au><au>Augustyniak-Bartosik, Hanna</au><au>Hurkacz, Magdalena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients—implications for therapeutic drug monitoring</atitle><jtitle>European journal of clinical pharmacology</jtitle><stitle>Eur J Clin Pharmacol</stitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2019-03</date><risdate>2019</risdate><volume>75</volume><issue>3</issue><spage>371</spage><epage>379</epage><pages>371-379</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Purpose
To evaluate the relationship between total and free MPA pharmacokinetic (PK) parameters and renal outcome markers, and to verify whether conducting therapeutic drug monitoring (TDM) in lupus nephritis (LN) patients would be of value in routine clinical practice.
Methods
Eighty-four samples were collected from sixteen LN patients. Total and free MPA concentrations were measured at predose, 0.5 and 2 h after mycophenolate mofetil (MMF) intake. Area under the concentration time curve from 0 to 2 h (AUC
0–2
) and free fraction were calculated.
Results
High between-patient variability was observed (CV% of 53.5% for dose-normalized total MPA AUC
0–2
). A significant but weak correlation between dose-normalized total C
0
and AUC
0–2
was noted (
r
= 0.5699). Dose-normalized total C
0
above 2.76 μg/mL·g may indicate patients with eGFR < 81 mL/min with sensitivity of 83.3% and specificity of 75.0%. Hypoalbuminemic LN patients demonstrated significantly elevated MPA free fraction when compared with patients with serum albumin concentration ≥ 3.5 g/dL (1.49 ± 0.64% vs 1.08 ± 0.75%).
Conclusion
This study examined relationship between free and total pharmacokinetic MPA parameters as well as the effect of hypoalbuminemia on MPA plasma protein binding in adult LN patients. The study results suggest that TDM of MPA in LN seems to be a more reasonable approach than the fixed-dose protocol. Moreover, predose total MPA concentration may be a possible estimation of MPA exposure, while monitoring free rather than total MPA may be more beneficial in hypoalbuminemic patients.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30430214</pmid><doi>10.1007/s00228-018-2599-x</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4622-8935</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of clinical pharmacology, 2019-03, Vol.75 (3), p.371-379 |
| issn | 0031-6970 1432-1041 |
| language | eng |
| recordid | cdi_proquest_journals_2133074147 |
| source | Springer Nature |
| subjects | Adult Area Under Curve Autoimmune diseases Biomedical and Life Sciences Biomedicine Concentration time Dose-Response Relationship, Drug Drug dosages Drug Monitoring Epidermal growth factor receptors Female Humans Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - blood Immunosuppressive Agents - therapeutic use Kidney - drug effects Kidney - metabolism Kidney Function Tests Lupus Lupus nephritis Lupus Nephritis - blood Lupus Nephritis - drug therapy Male Mycophenolate mofetil Mycophenolic acid Mycophenolic Acid - administration & dosage Mycophenolic Acid - blood Mycophenolic Acid - therapeutic use Nephritis Pharmacokinetics Pharmacokinetics and Disposition Pharmacology/Toxicology Therapeutic drug monitoring |
| title | Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients—implications for therapeutic drug monitoring |
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