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Cefazolin pharmacokinetics in premature infants
Objective Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants are virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth. Study Design We conducted a prospective, open-label PK and safety study of cefazolin in inf...
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| Published in: | Journal of perinatology 2019-09, Vol.39 (9), p.1213-1218 |
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| Main Authors: | , , , , , , , , |
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| container_end_page | 1218 |
| container_issue | 9 |
| container_start_page | 1213 |
| container_title | Journal of perinatology |
| container_volume | 39 |
| creator | Balevic, Stephen J. Smith, P. Brian Testoni, Daniela Wu, Huali Brouwer, Kim L. R. Zimmerman, Kanecia O. Rivera-Chaparro, Nazario D. Benjamin, Daniel K. Cohen-Wolkowiez, Michael |
| description | Objective
Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants are virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth.
Study Design
We conducted a prospective, open-label PK and safety study of cefazolin in infants ≤32 weeks gestation from a University Medical Center. We administered intravenous cefazolin and collected both timed and scavenged blood samples. We analyzed data using non-linear mixed effect modeling and simulated several dosage regimens to achieve target concentrations against methicillin-susceptible
Staphylococcus aureus
.
Results
We analyzed 40 samples from nine infants and observed that premature infants had lower clearance and greater volume of distribution for cefazolin compared to older children. The median (range) individual Bayesian estimates were 0.03 L/h/kg (0.01–0.08) for clearance and 0.39 L/kg (0.31–0.52) for volume.
Conclusion
Simulations suggested reduced cefazolin dosing based on postmenstrual age achieve target concentrations and potentially reduce unnecessary exposure. |
| doi_str_mv | 10.1038/s41372-019-0368-z |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_gale_infotracmisc_A597731390</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A597731390</galeid><sourcerecordid>A597731390</sourcerecordid><originalsourceid>FETCH-LOGICAL-c529t-4ceb48761677613d141eb478dc7fae9a5b9f13da0462fb86959017a8cbc6fd343</originalsourceid><addsrcrecordid>eNp1kUtLJDEUhYM4aPv4AW5EEAY3NSaV90aQxseAMBtdh1Q61V1albRJlWD_-rlFa9sOzCYh9373hHMPQicE_yKYqsvMCJVlgYkuMBWqWO2gCWFSFJwzuosmWDJaKMrEPjrI-RnjsSn30D7FmjGq1QRdTn1tV7FtwtlyYVNnXXxpgu8bl8_GWvKd7Yfk4VHb0Ocj9KO2bfbHH_cherq9eZzeFw9_7n5Prx8Kx0vdF8z5iikpiJBw0BlhBApSzZysrdeWV7qGssVMlHWlhOYaE2mVq5yoZ5TRQ3S11l0OVednzoc-2dYsU9PZ9G6ibcz3TmgWZh7fjJCEcqVB4OJDIMXXwefedE12vm1t8HHIpiwxBVJyDuj5P-hzHFIAe0ApUiqOJf2i5rb1BtYR4V83ipprrqUENY2B-rlFLbxt-0WO7dA3MeTvIFmDLsWck6833gg2Y7pmna6BdM2YrlnBzOn2UjYTn3ECUK6BDK0w9-nLyf9V_wJc7a59</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2281285073</pqid></control><display><type>article</type><title>Cefazolin pharmacokinetics in premature infants</title><source>Nexis Advance UK (Federated Access)</source><source>Springer Nature:Jisc Collections:Springer Nature Read and Publish 2023-2025: Springer Reading List</source><creator>Balevic, Stephen J. ; Smith, P. Brian ; Testoni, Daniela ; Wu, Huali ; Brouwer, Kim L. R. ; Zimmerman, Kanecia O. ; Rivera-Chaparro, Nazario D. ; Benjamin, Daniel K. ; Cohen-Wolkowiez, Michael</creator><creatorcontrib>Balevic, Stephen J. ; Smith, P. Brian ; Testoni, Daniela ; Wu, Huali ; Brouwer, Kim L. R. ; Zimmerman, Kanecia O. ; Rivera-Chaparro, Nazario D. ; Benjamin, Daniel K. ; Cohen-Wolkowiez, Michael</creatorcontrib><description>Objective
Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants are virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth.
Study Design
We conducted a prospective, open-label PK and safety study of cefazolin in infants ≤32 weeks gestation from a University Medical Center. We administered intravenous cefazolin and collected both timed and scavenged blood samples. We analyzed data using non-linear mixed effect modeling and simulated several dosage regimens to achieve target concentrations against methicillin-susceptible
Staphylococcus aureus
.
Results
We analyzed 40 samples from nine infants and observed that premature infants had lower clearance and greater volume of distribution for cefazolin compared to older children. The median (range) individual Bayesian estimates were 0.03 L/h/kg (0.01–0.08) for clearance and 0.39 L/kg (0.31–0.52) for volume.
Conclusion
Simulations suggested reduced cefazolin dosing based on postmenstrual age achieve target concentrations and potentially reduce unnecessary exposure.</description><identifier>ISSN: 0743-8346</identifier><identifier>ISSN: 1476-5543</identifier><identifier>EISSN: 1476-5543</identifier><identifier>DOI: 10.1038/s41372-019-0368-z</identifier><identifier>PMID: 30944398</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>692/700/1720 ; 692/700/565/1436/2774 ; Age ; Analysis ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - pharmacokinetics ; Antibiotics ; Bayesian analysis ; Cefazolin ; Cefazolin - administration & dosage ; Cefazolin - pharmacokinetics ; Computer simulation ; Creatinine ; Datasets as Topic ; Dosage ; Dosage and administration ; Drug dosages ; Drug therapy ; Female ; Gestation ; Gestational Age ; Health care facilities ; Humans ; Infant, Newborn ; Infant, Premature - blood ; Infant, Premature - metabolism ; Infants ; Infants (Premature) ; Intravenous administration ; Male ; Medicine ; Medicine & Public Health ; Methicillin ; Models, Biological ; Monte Carlo simulation ; Nonlinear analysis ; Pediatric Surgery ; Pediatrics ; Pharmacokinetics ; Pharmacology ; Population ; Premature babies ; Premature birth ; Prospective Studies</subject><ispartof>Journal of perinatology, 2019-09, Vol.39 (9), p.1213-1218</ispartof><rights>Springer Nature America, Inc. 2019</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Springer Nature America, Inc. 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-4ceb48761677613d141eb478dc7fae9a5b9f13da0462fb86959017a8cbc6fd343</citedby><cites>FETCH-LOGICAL-c529t-4ceb48761677613d141eb478dc7fae9a5b9f13da0462fb86959017a8cbc6fd343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30944398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Balevic, Stephen J.</creatorcontrib><creatorcontrib>Smith, P. Brian</creatorcontrib><creatorcontrib>Testoni, Daniela</creatorcontrib><creatorcontrib>Wu, Huali</creatorcontrib><creatorcontrib>Brouwer, Kim L. R.</creatorcontrib><creatorcontrib>Zimmerman, Kanecia O.</creatorcontrib><creatorcontrib>Rivera-Chaparro, Nazario D.</creatorcontrib><creatorcontrib>Benjamin, Daniel K.</creatorcontrib><creatorcontrib>Cohen-Wolkowiez, Michael</creatorcontrib><title>Cefazolin pharmacokinetics in premature infants</title><title>Journal of perinatology</title><addtitle>J Perinatol</addtitle><addtitle>J Perinatol</addtitle><description>Objective
Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants are virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth.
Study Design
We conducted a prospective, open-label PK and safety study of cefazolin in infants ≤32 weeks gestation from a University Medical Center. We administered intravenous cefazolin and collected both timed and scavenged blood samples. We analyzed data using non-linear mixed effect modeling and simulated several dosage regimens to achieve target concentrations against methicillin-susceptible
Staphylococcus aureus
.
Results
We analyzed 40 samples from nine infants and observed that premature infants had lower clearance and greater volume of distribution for cefazolin compared to older children. The median (range) individual Bayesian estimates were 0.03 L/h/kg (0.01–0.08) for clearance and 0.39 L/kg (0.31–0.52) for volume.
Conclusion
Simulations suggested reduced cefazolin dosing based on postmenstrual age achieve target concentrations and potentially reduce unnecessary exposure.</description><subject>692/700/1720</subject><subject>692/700/565/1436/2774</subject><subject>Age</subject><subject>Analysis</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Antibiotics</subject><subject>Bayesian analysis</subject><subject>Cefazolin</subject><subject>Cefazolin - administration & dosage</subject><subject>Cefazolin - pharmacokinetics</subject><subject>Computer simulation</subject><subject>Creatinine</subject><subject>Datasets as Topic</subject><subject>Dosage</subject><subject>Dosage and administration</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Gestation</subject><subject>Gestational Age</subject><subject>Health care facilities</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Infant, Premature - blood</subject><subject>Infant, Premature - metabolism</subject><subject>Infants</subject><subject>Infants (Premature)</subject><subject>Intravenous administration</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methicillin</subject><subject>Models, Biological</subject><subject>Monte Carlo simulation</subject><subject>Nonlinear analysis</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Population</subject><subject>Premature babies</subject><subject>Premature birth</subject><subject>Prospective Studies</subject><issn>0743-8346</issn><issn>1476-5543</issn><issn>1476-5543</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kUtLJDEUhYM4aPv4AW5EEAY3NSaV90aQxseAMBtdh1Q61V1albRJlWD_-rlFa9sOzCYh9373hHMPQicE_yKYqsvMCJVlgYkuMBWqWO2gCWFSFJwzuosmWDJaKMrEPjrI-RnjsSn30D7FmjGq1QRdTn1tV7FtwtlyYVNnXXxpgu8bl8_GWvKd7Yfk4VHb0Ocj9KO2bfbHH_cherq9eZzeFw9_7n5Prx8Kx0vdF8z5iikpiJBw0BlhBApSzZysrdeWV7qGssVMlHWlhOYaE2mVq5yoZ5TRQ3S11l0OVednzoc-2dYsU9PZ9G6ibcz3TmgWZh7fjJCEcqVB4OJDIMXXwefedE12vm1t8HHIpiwxBVJyDuj5P-hzHFIAe0ApUiqOJf2i5rb1BtYR4V83ipprrqUENY2B-rlFLbxt-0WO7dA3MeTvIFmDLsWck6833gg2Y7pmna6BdM2YrlnBzOn2UjYTn3ECUK6BDK0w9-nLyf9V_wJc7a59</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Balevic, Stephen J.</creator><creator>Smith, P. 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Brian</au><au>Testoni, Daniela</au><au>Wu, Huali</au><au>Brouwer, Kim L. R.</au><au>Zimmerman, Kanecia O.</au><au>Rivera-Chaparro, Nazario D.</au><au>Benjamin, Daniel K.</au><au>Cohen-Wolkowiez, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cefazolin pharmacokinetics in premature infants</atitle><jtitle>Journal of perinatology</jtitle><stitle>J Perinatol</stitle><addtitle>J Perinatol</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>39</volume><issue>9</issue><spage>1213</spage><epage>1218</epage><pages>1213-1218</pages><issn>0743-8346</issn><issn>1476-5543</issn><eissn>1476-5543</eissn><abstract>Objective
Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants are virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth.
Study Design
We conducted a prospective, open-label PK and safety study of cefazolin in infants ≤32 weeks gestation from a University Medical Center. We administered intravenous cefazolin and collected both timed and scavenged blood samples. We analyzed data using non-linear mixed effect modeling and simulated several dosage regimens to achieve target concentrations against methicillin-susceptible
Staphylococcus aureus
.
Results
We analyzed 40 samples from nine infants and observed that premature infants had lower clearance and greater volume of distribution for cefazolin compared to older children. The median (range) individual Bayesian estimates were 0.03 L/h/kg (0.01–0.08) for clearance and 0.39 L/kg (0.31–0.52) for volume.
Conclusion
Simulations suggested reduced cefazolin dosing based on postmenstrual age achieve target concentrations and potentially reduce unnecessary exposure.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30944398</pmid><doi>10.1038/s41372-019-0368-z</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0743-8346 |
| ispartof | Journal of perinatology, 2019-09, Vol.39 (9), p.1213-1218 |
| issn | 0743-8346 1476-5543 1476-5543 |
| language | eng |
| recordid | cdi_gale_infotracmisc_A597731390 |
| source | Nexis Advance UK (Federated Access); Springer Nature:Jisc Collections:Springer Nature Read and Publish 2023-2025: Springer Reading List |
| subjects | 692/700/1720 692/700/565/1436/2774 Age Analysis Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Antibiotics Bayesian analysis Cefazolin Cefazolin - administration & dosage Cefazolin - pharmacokinetics Computer simulation Creatinine Datasets as Topic Dosage Dosage and administration Drug dosages Drug therapy Female Gestation Gestational Age Health care facilities Humans Infant, Newborn Infant, Premature - blood Infant, Premature - metabolism Infants Infants (Premature) Intravenous administration Male Medicine Medicine & Public Health Methicillin Models, Biological Monte Carlo simulation Nonlinear analysis Pediatric Surgery Pediatrics Pharmacokinetics Pharmacology Population Premature babies Premature birth Prospective Studies |
| title | Cefazolin pharmacokinetics in premature infants |
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