Population Pharmacokinetics of Mycophenolic Acid: A Comparison between Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil in Renal Transplant Recipients
Objective: The pharmacokinetics of mycophenolic acid (MPA) were compared in renal transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). Methods: MPA concentration-time profiles were included from EC-MPS- (n = 208) and MMF-treated (n = 184)...
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| Veröffentlicht in: | Clinical pharmacokinetics 2008-01, Vol.47 (12), p.827-838 |
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| creator | de Winter, Brenda C. M. van Gelder, Teun Glander, Petra Cattaneo, Dario Tedesco-Silva, Helio Neumann, Irmgard Hilbrands, Luuk van Hest, Reinier M. Pescovitz, Mark D. Budde, Klemens Mathot, Ron A. A. |
| description | Objective:
The pharmacokinetics of mycophenolic acid (MPA) were compared in renal transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS).
Methods:
MPA concentration-time profiles were included from EC-MPS- (n = 208) and MMF-treated (n = 184) patients 4–257 months after renal transplantation. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling (NONMEM®). A two-compartment model with first-order absorption and elimination was used to describe the data.
Results:
No differences were detected in MPA clearance, intercompartmental clearance, or the central or peripheral volume of distribution. Respective values and interindividual variability (IIV) were 16 L/h (39%), 22 L/h (78%), 40 L (100%) and 518 L (490%). EC-MPS was absorbed more slowly than MMF with respective absorption rate constant values of 3.0 h
−1
and 4.1 h
−1
(p < 0.001) [IIV 187%]. A mixture model was used for the change-point parameter lag-time (t
lag
) in order to describe IIV in this parameter adequately for EC-MPS. Following the morning dose of EC-MPS, the tlag values were 0.95, 1.88 and 4.83 h for 51%, 32% and 17% of the population (IIV 8%), respectively. The morning tlag following EC-MPS administration was significantly different from both the tlag following MMF administration (0.30 h; p < 0.001 [IIV 11%]) and the t
lag
following the evening dose of EC-MPS (9.04 h; p < 0.001 [IIV 40%]). Post hoc analysis showed that the t
lag
was longer and more variable following EC-MPS administration (morning median 2.0 h [0.9–5.5 h], evening median 8.9 h [5.4–12.3 h]) than following MMF administration (median 0.30 h [0.26–0.34 h]; p < 0.001). The morning MPA predose concentrations were higher and more variable following EC-MPS administration than following MMF administration, with respective values of 2.6 mg/L (0.4–24.4 mg/L) and 1.6 mg/L (0.2–7.6 mg/L). The correlation between predose concentrations and the area under the plasma concentration-time curve (AUC) was lower in EC-MPS-treated patients (r
2
= 0.02) than in MMF-treated patients (r
2
= 0.48).
Conclusion:
Absorption of MPA was delayed and also slower following EC-MPS administration than following MMF administration. Furthermore, the t
lag
varied more in EC-MPS-treated patients. MPA predose concentrations were poorly correlated with the MPA AUC in both MMF- and EC-MPS-treated patients. |
| doi_str_mv | 10.2165/0003088-200847120-00007 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_222751605</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A199865914</galeid><sourcerecordid>A199865914</sourcerecordid><originalsourceid>FETCH-LOGICAL-c430t-cdaf158582369d7e032041b5d3412bc7776328306132bab078adbf97f59868283</originalsourceid><addsrcrecordid>eNqFkE1r3DAQhkVoSTYffyFdGnJ0OiNZX8clpB-Q0hzas5BlKVFiW1vJe8i_r9o1CYVC0UEw8zyj0UvIO4QrioJ_AAAGSjUUQLUSKTS1AvKArBClblBT8YasgCFtuBbsiByX8lgJVYVDcoQaqACmVgTu0nY32DmmaX33YPNoXXqKk5-jK-sU1l-fXdo--CkN0a03Lvan5G2wQ_Fny31Cfny8-X79ubn99unL9ea2cS2DuXG9DcgVV5QJ3UsPjEKLHe9Zi7RzUkrBqGIgkNHOdiCV7bugZeBaCVU7J-T9fu42p587X2bzmHZ5qk8aSqnkKIBX6GIP3dvBmziFNGfrxlic2aCuk7jGtlJX_6Dq6f0YXZp8iLX-lyD3gsuplOyD2eY42vxsEMzv_M2Sv3nJ3_zJv5rny9a7bvT9q7cEXoHLBbDF2SFkO7lYXjiKQJFJWjm150ptTfc-v37_fzv8AoJvmSA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222751605</pqid></control><display><type>article</type><title>Population Pharmacokinetics of Mycophenolic Acid: A Comparison between Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil in Renal Transplant Recipients</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>de Winter, Brenda C. M. ; van Gelder, Teun ; Glander, Petra ; Cattaneo, Dario ; Tedesco-Silva, Helio ; Neumann, Irmgard ; Hilbrands, Luuk ; van Hest, Reinier M. ; Pescovitz, Mark D. ; Budde, Klemens ; Mathot, Ron A. A.</creator><creatorcontrib>de Winter, Brenda C. M. ; van Gelder, Teun ; Glander, Petra ; Cattaneo, Dario ; Tedesco-Silva, Helio ; Neumann, Irmgard ; Hilbrands, Luuk ; van Hest, Reinier M. ; Pescovitz, Mark D. ; Budde, Klemens ; Mathot, Ron A. A.</creatorcontrib><description>Objective:
The pharmacokinetics of mycophenolic acid (MPA) were compared in renal transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS).
Methods:
MPA concentration-time profiles were included from EC-MPS- (n = 208) and MMF-treated (n = 184) patients 4–257 months after renal transplantation. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling (NONMEM®). A two-compartment model with first-order absorption and elimination was used to describe the data.
Results:
No differences were detected in MPA clearance, intercompartmental clearance, or the central or peripheral volume of distribution. Respective values and interindividual variability (IIV) were 16 L/h (39%), 22 L/h (78%), 40 L (100%) and 518 L (490%). EC-MPS was absorbed more slowly than MMF with respective absorption rate constant values of 3.0 h
−1
and 4.1 h
−1
(p < 0.001) [IIV 187%]. A mixture model was used for the change-point parameter lag-time (t
lag
) in order to describe IIV in this parameter adequately for EC-MPS. Following the morning dose of EC-MPS, the tlag values were 0.95, 1.88 and 4.83 h for 51%, 32% and 17% of the population (IIV 8%), respectively. The morning tlag following EC-MPS administration was significantly different from both the tlag following MMF administration (0.30 h; p < 0.001 [IIV 11%]) and the t
lag
following the evening dose of EC-MPS (9.04 h; p < 0.001 [IIV 40%]). Post hoc analysis showed that the t
lag
was longer and more variable following EC-MPS administration (morning median 2.0 h [0.9–5.5 h], evening median 8.9 h [5.4–12.3 h]) than following MMF administration (median 0.30 h [0.26–0.34 h]; p < 0.001). The morning MPA predose concentrations were higher and more variable following EC-MPS administration than following MMF administration, with respective values of 2.6 mg/L (0.4–24.4 mg/L) and 1.6 mg/L (0.2–7.6 mg/L). The correlation between predose concentrations and the area under the plasma concentration-time curve (AUC) was lower in EC-MPS-treated patients (r
2
= 0.02) than in MMF-treated patients (r
2
= 0.48).
Conclusion:
Absorption of MPA was delayed and also slower following EC-MPS administration than following MMF administration. Furthermore, the t
lag
varied more in EC-MPS-treated patients. MPA predose concentrations were poorly correlated with the MPA AUC in both MMF- and EC-MPS-treated patients.</description><identifier>ISSN: 0312-5963</identifier><identifier>EISSN: 1179-1926</identifier><identifier>DOI: 10.2165/0003088-200847120-00007</identifier><identifier>PMID: 19026038</identifier><identifier>CODEN: CPKNDH</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Administration, Oral ; Adult ; Aged ; Algorithms ; Area Under Curve ; Biological and medical sciences ; Clinical Trials as Topic ; Female ; Humans ; Immunomodulators ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - blood ; Immunosuppressive Agents - pharmacokinetics ; Internal Medicine ; Intestinal Absorption ; Kidney Transplantation ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Clearance Rate ; Middle Aged ; Models, Biological ; Mycophenolic Acid - administration & dosage ; Mycophenolic Acid - analogs & derivatives ; Mycophenolic Acid - blood ; Mycophenolic Acid - pharmacokinetics ; Original Research Article ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Pharmacotherapy ; Software ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the urinary system ; Tablets, Enteric-Coated ; Time Factors</subject><ispartof>Clinical pharmacokinetics, 2008-01, Vol.47 (12), p.827-838</ispartof><rights>Adis Data Information BV 2008</rights><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2008 Wolters Kluwer Health, Inc.</rights><rights>Copyright Wolters Kluwer Health Adis International 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c430t-cdaf158582369d7e032041b5d3412bc7776328306132bab078adbf97f59868283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.2165/0003088-200847120-00007$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.2165/0003088-200847120-00007$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21021372$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19026038$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Winter, Brenda C. M.</creatorcontrib><creatorcontrib>van Gelder, Teun</creatorcontrib><creatorcontrib>Glander, Petra</creatorcontrib><creatorcontrib>Cattaneo, Dario</creatorcontrib><creatorcontrib>Tedesco-Silva, Helio</creatorcontrib><creatorcontrib>Neumann, Irmgard</creatorcontrib><creatorcontrib>Hilbrands, Luuk</creatorcontrib><creatorcontrib>van Hest, Reinier M.</creatorcontrib><creatorcontrib>Pescovitz, Mark D.</creatorcontrib><creatorcontrib>Budde, Klemens</creatorcontrib><creatorcontrib>Mathot, Ron A. A.</creatorcontrib><title>Population Pharmacokinetics of Mycophenolic Acid: A Comparison between Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil in Renal Transplant Recipients</title><title>Clinical pharmacokinetics</title><addtitle>Clin Pharmacokinet</addtitle><addtitle>Clin Pharmacokinet</addtitle><description>Objective:
The pharmacokinetics of mycophenolic acid (MPA) were compared in renal transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS).
Methods:
MPA concentration-time profiles were included from EC-MPS- (n = 208) and MMF-treated (n = 184) patients 4–257 months after renal transplantation. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling (NONMEM®). A two-compartment model with first-order absorption and elimination was used to describe the data.
Results:
No differences were detected in MPA clearance, intercompartmental clearance, or the central or peripheral volume of distribution. Respective values and interindividual variability (IIV) were 16 L/h (39%), 22 L/h (78%), 40 L (100%) and 518 L (490%). EC-MPS was absorbed more slowly than MMF with respective absorption rate constant values of 3.0 h
−1
and 4.1 h
−1
(p < 0.001) [IIV 187%]. A mixture model was used for the change-point parameter lag-time (t
lag
) in order to describe IIV in this parameter adequately for EC-MPS. Following the morning dose of EC-MPS, the tlag values were 0.95, 1.88 and 4.83 h for 51%, 32% and 17% of the population (IIV 8%), respectively. The morning tlag following EC-MPS administration was significantly different from both the tlag following MMF administration (0.30 h; p < 0.001 [IIV 11%]) and the t
lag
following the evening dose of EC-MPS (9.04 h; p < 0.001 [IIV 40%]). Post hoc analysis showed that the t
lag
was longer and more variable following EC-MPS administration (morning median 2.0 h [0.9–5.5 h], evening median 8.9 h [5.4–12.3 h]) than following MMF administration (median 0.30 h [0.26–0.34 h]; p < 0.001). The morning MPA predose concentrations were higher and more variable following EC-MPS administration than following MMF administration, with respective values of 2.6 mg/L (0.4–24.4 mg/L) and 1.6 mg/L (0.2–7.6 mg/L). The correlation between predose concentrations and the area under the plasma concentration-time curve (AUC) was lower in EC-MPS-treated patients (r
2
= 0.02) than in MMF-treated patients (r
2
= 0.48).
Conclusion:
Absorption of MPA was delayed and also slower following EC-MPS administration than following MMF administration. Furthermore, the t
lag
varied more in EC-MPS-treated patients. MPA predose concentrations were poorly correlated with the MPA AUC in both MMF- and EC-MPS-treated patients.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Aged</subject><subject>Algorithms</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>Clinical Trials as Topic</subject><subject>Female</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - blood</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Internal Medicine</subject><subject>Intestinal Absorption</subject><subject>Kidney Transplantation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Clearance Rate</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Mycophenolic Acid - administration & dosage</subject><subject>Mycophenolic Acid - analogs & derivatives</subject><subject>Mycophenolic Acid - blood</subject><subject>Mycophenolic Acid - pharmacokinetics</subject><subject>Original Research Article</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Software</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>Tablets, Enteric-Coated</subject><subject>Time Factors</subject><issn>0312-5963</issn><issn>1179-1926</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkE1r3DAQhkVoSTYffyFdGnJ0OiNZX8clpB-Q0hzas5BlKVFiW1vJe8i_r9o1CYVC0UEw8zyj0UvIO4QrioJ_AAAGSjUUQLUSKTS1AvKArBClblBT8YasgCFtuBbsiByX8lgJVYVDcoQaqACmVgTu0nY32DmmaX33YPNoXXqKk5-jK-sU1l-fXdo--CkN0a03Lvan5G2wQ_Fny31Cfny8-X79ubn99unL9ea2cS2DuXG9DcgVV5QJ3UsPjEKLHe9Zi7RzUkrBqGIgkNHOdiCV7bugZeBaCVU7J-T9fu42p587X2bzmHZ5qk8aSqnkKIBX6GIP3dvBmziFNGfrxlic2aCuk7jGtlJX_6Dq6f0YXZp8iLX-lyD3gsuplOyD2eY42vxsEMzv_M2Sv3nJ3_zJv5rny9a7bvT9q7cEXoHLBbDF2SFkO7lYXjiKQJFJWjm150ptTfc-v37_fzv8AoJvmSA</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>de Winter, Brenda C. M.</creator><creator>van Gelder, Teun</creator><creator>Glander, Petra</creator><creator>Cattaneo, Dario</creator><creator>Tedesco-Silva, Helio</creator><creator>Neumann, Irmgard</creator><creator>Hilbrands, Luuk</creator><creator>van Hest, Reinier M.</creator><creator>Pescovitz, Mark D.</creator><creator>Budde, Klemens</creator><creator>Mathot, Ron A. A.</creator><general>Springer International Publishing</general><general>Adis International</general><general>Wolters Kluwer Health, Inc</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>4T-</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20080101</creationdate><title>Population Pharmacokinetics of Mycophenolic Acid</title><author>de Winter, Brenda C. M. ; van Gelder, Teun ; Glander, Petra ; Cattaneo, Dario ; Tedesco-Silva, Helio ; Neumann, Irmgard ; Hilbrands, Luuk ; van Hest, Reinier M. ; Pescovitz, Mark D. ; Budde, Klemens ; Mathot, Ron A. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-cdaf158582369d7e032041b5d3412bc7776328306132bab078adbf97f59868283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Aged</topic><topic>Algorithms</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>Clinical Trials as Topic</topic><topic>Female</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - blood</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Internal Medicine</topic><topic>Intestinal Absorption</topic><topic>Kidney Transplantation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Clearance Rate</topic><topic>Middle Aged</topic><topic>Models, Biological</topic><topic>Mycophenolic Acid - administration & dosage</topic><topic>Mycophenolic Acid - analogs & derivatives</topic><topic>Mycophenolic Acid - blood</topic><topic>Mycophenolic Acid - pharmacokinetics</topic><topic>Original Research Article</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Software</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>Tablets, Enteric-Coated</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Winter, Brenda C. M.</creatorcontrib><creatorcontrib>van Gelder, Teun</creatorcontrib><creatorcontrib>Glander, Petra</creatorcontrib><creatorcontrib>Cattaneo, Dario</creatorcontrib><creatorcontrib>Tedesco-Silva, Helio</creatorcontrib><creatorcontrib>Neumann, Irmgard</creatorcontrib><creatorcontrib>Hilbrands, Luuk</creatorcontrib><creatorcontrib>van Hest, Reinier M.</creatorcontrib><creatorcontrib>Pescovitz, Mark D.</creatorcontrib><creatorcontrib>Budde, Klemens</creatorcontrib><creatorcontrib>Mathot, Ron A. A.</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>Docstoc</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>Clinical pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Winter, Brenda C. M.</au><au>van Gelder, Teun</au><au>Glander, Petra</au><au>Cattaneo, Dario</au><au>Tedesco-Silva, Helio</au><au>Neumann, Irmgard</au><au>Hilbrands, Luuk</au><au>van Hest, Reinier M.</au><au>Pescovitz, Mark D.</au><au>Budde, Klemens</au><au>Mathot, Ron A. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Population Pharmacokinetics of Mycophenolic Acid: A Comparison between Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil in Renal Transplant Recipients</atitle><jtitle>Clinical pharmacokinetics</jtitle><stitle>Clin Pharmacokinet</stitle><addtitle>Clin Pharmacokinet</addtitle><date>2008-01-01</date><risdate>2008</risdate><volume>47</volume><issue>12</issue><spage>827</spage><epage>838</epage><pages>827-838</pages><issn>0312-5963</issn><eissn>1179-1926</eissn><coden>CPKNDH</coden><abstract>Objective:
The pharmacokinetics of mycophenolic acid (MPA) were compared in renal transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS).
Methods:
MPA concentration-time profiles were included from EC-MPS- (n = 208) and MMF-treated (n = 184) patients 4–257 months after renal transplantation. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling (NONMEM®). A two-compartment model with first-order absorption and elimination was used to describe the data.
Results:
No differences were detected in MPA clearance, intercompartmental clearance, or the central or peripheral volume of distribution. Respective values and interindividual variability (IIV) were 16 L/h (39%), 22 L/h (78%), 40 L (100%) and 518 L (490%). EC-MPS was absorbed more slowly than MMF with respective absorption rate constant values of 3.0 h
−1
and 4.1 h
−1
(p < 0.001) [IIV 187%]. A mixture model was used for the change-point parameter lag-time (t
lag
) in order to describe IIV in this parameter adequately for EC-MPS. Following the morning dose of EC-MPS, the tlag values were 0.95, 1.88 and 4.83 h for 51%, 32% and 17% of the population (IIV 8%), respectively. The morning tlag following EC-MPS administration was significantly different from both the tlag following MMF administration (0.30 h; p < 0.001 [IIV 11%]) and the t
lag
following the evening dose of EC-MPS (9.04 h; p < 0.001 [IIV 40%]). Post hoc analysis showed that the t
lag
was longer and more variable following EC-MPS administration (morning median 2.0 h [0.9–5.5 h], evening median 8.9 h [5.4–12.3 h]) than following MMF administration (median 0.30 h [0.26–0.34 h]; p < 0.001). The morning MPA predose concentrations were higher and more variable following EC-MPS administration than following MMF administration, with respective values of 2.6 mg/L (0.4–24.4 mg/L) and 1.6 mg/L (0.2–7.6 mg/L). The correlation between predose concentrations and the area under the plasma concentration-time curve (AUC) was lower in EC-MPS-treated patients (r
2
= 0.02) than in MMF-treated patients (r
2
= 0.48).
Conclusion:
Absorption of MPA was delayed and also slower following EC-MPS administration than following MMF administration. Furthermore, the t
lag
varied more in EC-MPS-treated patients. MPA predose concentrations were poorly correlated with the MPA AUC in both MMF- and EC-MPS-treated patients.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>19026038</pmid><doi>10.2165/0003088-200847120-00007</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0312-5963 |
| ispartof | Clinical pharmacokinetics, 2008-01, Vol.47 (12), p.827-838 |
| issn | 0312-5963 1179-1926 |
| language | eng |
| recordid | cdi_proquest_journals_222751605 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Administration, Oral Adult Aged Algorithms Area Under Curve Biological and medical sciences Clinical Trials as Topic Female Humans Immunomodulators Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - blood Immunosuppressive Agents - pharmacokinetics Internal Medicine Intestinal Absorption Kidney Transplantation Male Medical sciences Medicine Medicine & Public Health Metabolic Clearance Rate Middle Aged Models, Biological Mycophenolic Acid - administration & dosage Mycophenolic Acid - analogs & derivatives Mycophenolic Acid - blood Mycophenolic Acid - pharmacokinetics Original Research Article Pharmacology. Drug treatments Pharmacology/Toxicology Pharmacotherapy Software Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system Tablets, Enteric-Coated Time Factors |
| title | Population Pharmacokinetics of Mycophenolic Acid: A Comparison between Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil in Renal Transplant Recipients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T01%3A31%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Population%20Pharmacokinetics%20of%20Mycophenolic%20Acid:%20A%20Comparison%20between%20Enteric-Coated%20Mycophenolate%20Sodium%20and%20Mycophenolate%20Mofetil%20in%20Renal%20Transplant%20Recipients&rft.jtitle=Clinical%20pharmacokinetics&rft.au=de%20Winter,%20Brenda%20C.%20M.&rft.date=2008-01-01&rft.volume=47&rft.issue=12&rft.spage=827&rft.epage=838&rft.pages=827-838&rft.issn=0312-5963&rft.eissn=1179-1926&rft.coden=CPKNDH&rft_id=info:doi/10.2165/0003088-200847120-00007&rft_dat=%3Cgale_proqu%3EA199865914%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222751605&rft_id=info:pmid/19026038&rft_galeid=A199865914&rfr_iscdi=true |