Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy
To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations. This was a hospital-based clinic...
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| Veröffentlicht in: | Clinical microbiology and infection 2017-09, Vol.23 (9), p.674.e7-674.e13 |
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| creator | Byrne, C.J. Roberts, J.A. McWhinney, B. Ryder, S.A. Fennell, J.P. O'Byrne, P. Deasy, E. Egan, S. Desmond, R. Enright, H. D'Arcy, D.M. McHugh, J. |
| description | To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations.
This was a hospital-based clinical trial (EudraCT 2013–004535–72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics.
Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC48–72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC48–72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p |
| doi_str_mv | 10.1016/j.cmi.2017.02.032 |
| format | Article |
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This was a hospital-based clinical trial (EudraCT 2013–004535–72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics.
Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC48–72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC48–72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours.
To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended.</description><identifier>ISSN: 1198-743X</identifier><identifier>EISSN: 1469-0691</identifier><identifier>DOI: 10.1016/j.cmi.2017.02.032</identifier><identifier>PMID: 28267636</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Aged ; Anti-Bacterial Agents - blood ; Anti-Bacterial Agents - pharmacokinetics ; Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; Drug Monitoring ; Female ; Glycopeptides ; Gram-Positive Bacterial Infections - drug therapy ; Gram-Positive Bacterial Infections - prevention & control ; Haematological malignancy ; Hematologic Neoplasms - epidemiology ; Humans ; Male ; Middle Aged ; Monte Carlo simulations ; Population pharmacokinetics ; Prospective Studies ; Teicoplanin ; Teicoplanin - blood ; Teicoplanin - pharmacokinetics ; Teicoplanin - pharmacology ; Teicoplanin - therapeutic use ; Therapeutic drug monitoring</subject><ispartof>Clinical microbiology and infection, 2017-09, Vol.23 (9), p.674.e7-674.e13</ispartof><rights>2017 European Society of Clinical Microbiology and Infectious Diseases</rights><rights>Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-fb23711d971be83a6579a3b0ea7a7c060feba0a6899ba7f92de3631a6b2b36833</citedby><cites>FETCH-LOGICAL-c396t-fb23711d971be83a6579a3b0ea7a7c060feba0a6899ba7f92de3631a6b2b36833</cites></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/28267636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Byrne, C.J.</creatorcontrib><creatorcontrib>Roberts, J.A.</creatorcontrib><creatorcontrib>McWhinney, B.</creatorcontrib><creatorcontrib>Ryder, S.A.</creatorcontrib><creatorcontrib>Fennell, J.P.</creatorcontrib><creatorcontrib>O'Byrne, P.</creatorcontrib><creatorcontrib>Deasy, E.</creatorcontrib><creatorcontrib>Egan, S.</creatorcontrib><creatorcontrib>Desmond, R.</creatorcontrib><creatorcontrib>Enright, H.</creatorcontrib><creatorcontrib>D'Arcy, D.M.</creatorcontrib><creatorcontrib>McHugh, J.</creatorcontrib><title>Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy</title><title>Clinical microbiology and infection</title><addtitle>Clin Microbiol Infect</addtitle><description>To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations.
This was a hospital-based clinical trial (EudraCT 2013–004535–72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics.
Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC48–72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC48–72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours.
To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended.</description><subject>Aged</subject><subject>Anti-Bacterial Agents - blood</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Drug Monitoring</subject><subject>Female</subject><subject>Glycopeptides</subject><subject>Gram-Positive Bacterial Infections - drug therapy</subject><subject>Gram-Positive Bacterial Infections - prevention & control</subject><subject>Haematological malignancy</subject><subject>Hematologic Neoplasms - epidemiology</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monte Carlo simulations</subject><subject>Population pharmacokinetics</subject><subject>Prospective Studies</subject><subject>Teicoplanin</subject><subject>Teicoplanin - blood</subject><subject>Teicoplanin - pharmacokinetics</subject><subject>Teicoplanin - pharmacology</subject><subject>Teicoplanin - therapeutic use</subject><subject>Therapeutic drug monitoring</subject><issn>1198-743X</issn><issn>1469-0691</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAURi1ERUvhAdggL9kk9c_UjsUKVVCQKtFFK7GzbpybGQ-JHWKnaJ6EbZ-lT1aPpmXBgpVt-TufdX0IecdZzRlXZ9vajb4WjOuaiZpJ8YKc8JUyFVOGvyx7bppKr-SPY_I6pS1jTEi5ekWORSOUVlKdkD_XcVoGyD4GOm1gHsHFnz5g9i7R2NOM3sVpgOADhdBRyBl8GDHkcvtw_w9y9nzudgFG72iGeY050T3dLUOmU3mqwIn-9nnzcL8BHCHHIa69g4GOMPh1gOB2b8hRD0PCt0_rKbn98vnm4mt19f3y28Wnq8pJo3LVt0JqzjujeYuNBHWuDciWIWjQjinWYwsMVGNMC7o3okOpJAfVilaqRspT8uHQO83x14Ip29Enh0OZGOOSLG_0uTTGNKsS5Yeom2NKM_Z2mv0I885yZvc-7NYWH3bvwzJhi4_CvH-qX9oRu7_Es4AS-HgIYBnyzuNskysf5LDzM7psu-j_U_8IZH6iTQ</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Byrne, C.J.</creator><creator>Roberts, J.A.</creator><creator>McWhinney, B.</creator><creator>Ryder, S.A.</creator><creator>Fennell, J.P.</creator><creator>O'Byrne, P.</creator><creator>Deasy, E.</creator><creator>Egan, S.</creator><creator>Desmond, R.</creator><creator>Enright, H.</creator><creator>D'Arcy, D.M.</creator><creator>McHugh, J.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>201709</creationdate><title>Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy</title><author>Byrne, C.J. ; 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This was a hospital-based clinical trial (EudraCT 2013–004535–72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics.
Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC48–72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC48–72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours.
To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28267636</pmid><doi>10.1016/j.cmi.2017.02.032</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical microbiology and infection, 2017-09, Vol.23 (9), p.674.e7-674.e13 |
| issn | 1198-743X 1469-0691 |
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| subjects | Aged Anti-Bacterial Agents - blood Anti-Bacterial Agents - pharmacokinetics Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Drug Monitoring Female Glycopeptides Gram-Positive Bacterial Infections - drug therapy Gram-Positive Bacterial Infections - prevention & control Haematological malignancy Hematologic Neoplasms - epidemiology Humans Male Middle Aged Monte Carlo simulations Population pharmacokinetics Prospective Studies Teicoplanin Teicoplanin - blood Teicoplanin - pharmacokinetics Teicoplanin - pharmacology Teicoplanin - therapeutic use Therapeutic drug monitoring |
| title | Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy |
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