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A Population Pharmacokinetic Approach to Describe Cephalexin Disposition in Adult and Aged Dogs
This study was conducted in order to characterize the pharmacokinetics of orally administered cephalexin to healthy adult and aged dogs, using a population pharmacokinetic approach. Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used....
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Published in: | Veterinary medicine international 2014, Vol.2014 (2014), p.1-7 |
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creator | Rebuelto, Marcela Tarragona, Lisa Quaine, Pamela Monfrinotti, Agustina Kreil, Verónica Schaiquevich, Paula Prados, Ana Paula Hallu, Ruben |
description | This study was conducted in order to characterize the pharmacokinetics of orally administered cephalexin to healthy adult and aged dogs, using a population pharmacokinetic approach. Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used. Sex, age, pharmaceutical formulation, and breed were evaluated as covariates. A one-compartment model with an absorption lag-time (Tlag) best described the data. The final model included age (adult; aged) on apparent volume of distribution (Vd/F), apparent elimination rate (ke/F), and Tlag; sex (female; male) on ke/F, and breed (Beagle; mixed-breed) on Vd/F. Addition of the covariates to the model explained 78% of the interindividal variability (IIV) in Vd/F, 36% in ke/F, and 24% in Tlag, respectively. Formulation did not affect the variability of any of the pharmacokinetic parameters. Tlag was longer, whereas Vd/F and ke/F were lower in aged compared to adult animals; in female aged dogs ke/F was lower than in male aged dogs; however, the differences were of low magnitude. Different disposition of cephalexin may be expected in aged dogs. |
doi_str_mv | 10.1155/2014/789353 |
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Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used. Sex, age, pharmaceutical formulation, and breed were evaluated as covariates. A one-compartment model with an absorption lag-time (Tlag) best described the data. The final model included age (adult; aged) on apparent volume of distribution (Vd/F), apparent elimination rate (ke/F), and Tlag; sex (female; male) on ke/F, and breed (Beagle; mixed-breed) on Vd/F. Addition of the covariates to the model explained 78% of the interindividal variability (IIV) in Vd/F, 36% in ke/F, and 24% in Tlag, respectively. Formulation did not affect the variability of any of the pharmacokinetic parameters. Tlag was longer, whereas Vd/F and ke/F were lower in aged compared to adult animals; in female aged dogs ke/F was lower than in male aged dogs; however, the differences were of low magnitude. Different disposition of cephalexin may be expected in aged dogs.</description><identifier>ISSN: 2090-8113</identifier><identifier>ISSN: 2042-0048</identifier><identifier>EISSN: 2042-0048</identifier><identifier>DOI: 10.1155/2014/789353</identifier><identifier>PMID: 25431741</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Antibiotics ; Aqueous solutions ; Cephalexin ; Complications and side effects ; Dogs ; Dosage and administration ; Drug dosages ; Genetic aspects ; Geriatrics ; Pharmacokinetics ; Physiological aspects ; Population ; Rodents ; Studies ; Veterinary medicine</subject><ispartof>Veterinary medicine international, 2014, Vol.2014 (2014), p.1-7</ispartof><rights>Copyright © 2014 Ana Paula Prados et al.</rights><rights>COPYRIGHT 2014 Hindawi Limited</rights><rights>Copyright © 2014 Ana Paula Prados et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Ana Paula Prados et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5153-64c6a4c204ed39b84d24c0a6519f0bac78272724a38eea17dc51e1062a20bfdc3</citedby><cites>FETCH-LOGICAL-c5153-64c6a4c204ed39b84d24c0a6519f0bac78272724a38eea17dc51e1062a20bfdc3</cites><orcidid>0000-0002-2568-4731 ; 0000-0001-9567-1365</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1709494956/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1709494956?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,25753,27923,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25431741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Virkel, Guillermo</contributor><creatorcontrib>Rebuelto, Marcela</creatorcontrib><creatorcontrib>Tarragona, Lisa</creatorcontrib><creatorcontrib>Quaine, Pamela</creatorcontrib><creatorcontrib>Monfrinotti, Agustina</creatorcontrib><creatorcontrib>Kreil, Verónica</creatorcontrib><creatorcontrib>Schaiquevich, Paula</creatorcontrib><creatorcontrib>Prados, Ana Paula</creatorcontrib><creatorcontrib>Hallu, Ruben</creatorcontrib><title>A Population Pharmacokinetic Approach to Describe Cephalexin Disposition in Adult and Aged Dogs</title><title>Veterinary medicine international</title><addtitle>Vet Med Int</addtitle><description>This study was conducted in order to characterize the pharmacokinetics of orally administered cephalexin to healthy adult and aged dogs, using a population pharmacokinetic approach. Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used. Sex, age, pharmaceutical formulation, and breed were evaluated as covariates. A one-compartment model with an absorption lag-time (Tlag) best described the data. The final model included age (adult; aged) on apparent volume of distribution (Vd/F), apparent elimination rate (ke/F), and Tlag; sex (female; male) on ke/F, and breed (Beagle; mixed-breed) on Vd/F. Addition of the covariates to the model explained 78% of the interindividal variability (IIV) in Vd/F, 36% in ke/F, and 24% in Tlag, respectively. Formulation did not affect the variability of any of the pharmacokinetic parameters. Tlag was longer, whereas Vd/F and ke/F were lower in aged compared to adult animals; in female aged dogs ke/F was lower than in male aged dogs; however, the differences were of low magnitude. Different disposition of cephalexin may be expected in aged dogs.</description><subject>Antibiotics</subject><subject>Aqueous solutions</subject><subject>Cephalexin</subject><subject>Complications and side effects</subject><subject>Dogs</subject><subject>Dosage and administration</subject><subject>Drug dosages</subject><subject>Genetic aspects</subject><subject>Geriatrics</subject><subject>Pharmacokinetics</subject><subject>Physiological aspects</subject><subject>Population</subject><subject>Rodents</subject><subject>Studies</subject><subject>Veterinary medicine</subject><issn>2090-8113</issn><issn>2042-0048</issn><issn>2042-0048</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNkstv1DAQhyMEotXSE3cUiQsCbetn4lyQol0elSrRA5ytiT3Z9ZKNg50U-O_xNqV0EQc8B7---XlmPFn2nJJzSqW8YISKi1JVXPJH2Skjgi0JEerxYV2RpaKUn2RnMe5IGpxVjFdPsxMmBaeloKeZrvNrP0wdjM73-fUWwh6M_-p6HJ3J62EIHsw2H32-xmiCazBf4bCFDn-4Pl-7OPjobn3TtrZTN-bQ27zeoM3XfhOfZU9a6CKe3c2L7Mv7d59XH5dXnz5cruqrpZFU8mUhTAHCpPjR8qpRwjJhCBSSVi1pwJSKlckEcIUItLTJDSkpGDDStNbwRXY561oPOz0Et4fwU3tw-vbAh42GkFLqUAvZloUSrTFQiUpYkBTAMgWCN4qjSlpvZ61havZoDfZjgO5I9Pimd1u98TdaMEGZZEng1Z1A8N8mjKPeu2iw66BHP0VNC15KqRitEvryL3Tnp9CnUmlakkN8lSz-UJtUeO361qd3zUFU14KxijCefnSRnf-DSmZx74zvsXXp_Mjhzexggo8xYHufIyX60F760F56bq9Ev3hYlnv2dzMl4PUMbF1v4bv7PzVMCLbwAE6fLiT_BYGT3kc</recordid><startdate>2014</startdate><enddate>2014</enddate><creator>Rebuelto, Marcela</creator><creator>Tarragona, Lisa</creator><creator>Quaine, Pamela</creator><creator>Monfrinotti, Agustina</creator><creator>Kreil, Verónica</creator><creator>Schaiquevich, Paula</creator><creator>Prados, Ana Paula</creator><creator>Hallu, Ruben</creator><general>Hindawi Publishing Corporation</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RQ</scope><scope>7T5</scope><scope>7TM</scope><scope>7U9</scope><scope>7XB</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>M2O</scope><scope>M7N</scope><scope>MBDVC</scope><scope>PADUT</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>U9A</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2568-4731</orcidid><orcidid>https://orcid.org/0000-0001-9567-1365</orcidid></search><sort><creationdate>2014</creationdate><title>A Population Pharmacokinetic Approach to Describe Cephalexin Disposition in Adult and Aged Dogs</title><author>Rebuelto, Marcela ; 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Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used. Sex, age, pharmaceutical formulation, and breed were evaluated as covariates. A one-compartment model with an absorption lag-time (Tlag) best described the data. The final model included age (adult; aged) on apparent volume of distribution (Vd/F), apparent elimination rate (ke/F), and Tlag; sex (female; male) on ke/F, and breed (Beagle; mixed-breed) on Vd/F. Addition of the covariates to the model explained 78% of the interindividal variability (IIV) in Vd/F, 36% in ke/F, and 24% in Tlag, respectively. Formulation did not affect the variability of any of the pharmacokinetic parameters. Tlag was longer, whereas Vd/F and ke/F were lower in aged compared to adult animals; in female aged dogs ke/F was lower than in male aged dogs; however, the differences were of low magnitude. Different disposition of cephalexin may be expected in aged dogs.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>25431741</pmid><doi>10.1155/2014/789353</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-2568-4731</orcidid><orcidid>https://orcid.org/0000-0001-9567-1365</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antibiotics Aqueous solutions Cephalexin Complications and side effects Dogs Dosage and administration Drug dosages Genetic aspects Geriatrics Pharmacokinetics Physiological aspects Population Rodents Studies Veterinary medicine |
title | A Population Pharmacokinetic Approach to Describe Cephalexin Disposition in Adult and Aged Dogs |
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