The bioavailability and maturing clearance of doxapram in preterm infants
Background Doxapram is used for the treatment of apnea of prematurity in dosing regimens only based on bodyweight, as pharmacokinetic data are limited. This study describes the pharmacokinetics of doxapram and keto-doxapram in preterm infants. Methods Data (302 samples) from 75 neonates were include...
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| Veröffentlicht in: | Pediatric research 2021-04, Vol.89 (5), p.1268-1277 |
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| creator | Flint, Robert B. Simons, Sinno H. P. Andriessen, Peter Liem, Kian D. Degraeuwe, Pieter L. J. Reiss, Irwin K. M. Ter Heine, Rob Engbers, Aline G. J. Koch, Birgit C. P. Groot, Ronald de Burger, David M. Knibbe, Catherijne A. J. Völler, Swantje |
| description | Background
Doxapram is used for the treatment of apnea of prematurity in dosing regimens only based on bodyweight, as pharmacokinetic data are limited. This study describes the pharmacokinetics of doxapram and keto-doxapram in preterm infants.
Methods
Data (302 samples) from 75 neonates were included with a median (range) gestational age (GA) 25.9 (23.9–29.4) weeks, bodyweight 0.95 (0.48–1.61) kg, and postnatal age (PNA) 17 (1–52) days at the start of continuous treatment. A population pharmacokinetic model was developed using non-linear mixed-effects modelling (NONMEM®).
Results
A two-compartment model best described the pharmacokinetics of doxapram and keto-doxapram. PNA and GA affected the formation clearance of keto-doxapram (CL
FORMATION KETO-DOXAPRAM
) and clearance of doxapram via other routes (CL
DOXAPRAM OTHER ROUTES
). For a median individual of 0.95 kg, GA 25.6 weeks, and PNA 29 days, CL
FORMATION KETO-DOXAPRAM
was 0.115 L/h (relative standard error (RSE) 12%) and CL
DOXAPRAM OTHER ROUTES
was 0.645 L/h (RSE 9%). Oral bioavailability was estimated at 74% (RSE 10%).
Conclusions
Dosing of doxapram only based on bodyweight results in the highest exposure in preterm infants with the lowest PNA and GA. Therefore, dosing may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. For switching to oral therapy, a 33% dose increase is required to maintain exposure.
Impact
Current dosing regimens of doxapram in preterm infants only based on bodyweight result in the highest exposure in infants with the lowest PNA and GA.
Dosing of doxapram may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events.
Describing the pharmacokinetics of doxapram and its active metabolite keto-doxapram following intravenous and gastroenteral administration enables to include drug exposure to the evaluation of treatment of AOP.
The oral bioavailability of doxapram in preterm neonates is 74%, requiring a 33% higher dose via oral than intravenous administration to maintain exposure. |
| doi_str_mv | 10.1038/s41390-020-1037-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2526476513</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2526476513</sourcerecordid><originalsourceid>FETCH-LOGICAL-c415t-57cc96923b0c1ecbe893de100f44bf9d321b95c59dca7b37e5a9de05089333103</originalsourceid><addsrcrecordid>eNp1kE1PxCAQhonRuOvqD_BiSDyjUKAtR7PxY5NNvKxnAnSq3fRLaI3-e2m66snTzJBn3gkPQpeM3jDK89sgGFeU0ISSOGdEHaElkzy-CJEdoyWlnBGuVL5AZyHsKWVC5uIULXiSqpwpvkSb3RtgW3Xmw1S1sVVdDV_YtAVuzDD6qn3FrgbjTesAdyUuuk_Te9PgqsW9hwH81JamHcI5OilNHeDiUFfo5eF-t34i2-fHzfpuS5xgciAyc06lKuGWOgbOQq54AYzSUghbqoInzCrppCqcySzPQBpVAJU0cpzHb67Q9Zzb--59hDDofTf6Np7UiUxSkaWS8UixmXK-C8FDqXtfNcZ_aUb1JE_P8nSUN82ZVnHn6pA82gaK340fWxFIZiD0kxrwf6f_T_0GTfB5gg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2526476513</pqid></control><display><type>article</type><title>The bioavailability and maturing clearance of doxapram in preterm infants</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Flint, Robert B. ; Simons, Sinno H. P. ; Andriessen, Peter ; Liem, Kian D. ; Degraeuwe, Pieter L. J. ; Reiss, Irwin K. M. ; Ter Heine, Rob ; Engbers, Aline G. J. ; Koch, Birgit C. P. ; Groot, Ronald de ; Burger, David M. ; Knibbe, Catherijne A. J. ; Völler, Swantje</creator><creatorcontrib>Flint, Robert B. ; Simons, Sinno H. P. ; Andriessen, Peter ; Liem, Kian D. ; Degraeuwe, Pieter L. J. ; Reiss, Irwin K. M. ; Ter Heine, Rob ; Engbers, Aline G. J. ; Koch, Birgit C. P. ; Groot, Ronald de ; Burger, David M. ; Knibbe, Catherijne A. J. ; Völler, Swantje ; DINO Research Group ; DINO Research Group</creatorcontrib><description>Background
Doxapram is used for the treatment of apnea of prematurity in dosing regimens only based on bodyweight, as pharmacokinetic data are limited. This study describes the pharmacokinetics of doxapram and keto-doxapram in preterm infants.
Methods
Data (302 samples) from 75 neonates were included with a median (range) gestational age (GA) 25.9 (23.9–29.4) weeks, bodyweight 0.95 (0.48–1.61) kg, and postnatal age (PNA) 17 (1–52) days at the start of continuous treatment. A population pharmacokinetic model was developed using non-linear mixed-effects modelling (NONMEM®).
Results
A two-compartment model best described the pharmacokinetics of doxapram and keto-doxapram. PNA and GA affected the formation clearance of keto-doxapram (CL
FORMATION KETO-DOXAPRAM
) and clearance of doxapram via other routes (CL
DOXAPRAM OTHER ROUTES
). For a median individual of 0.95 kg, GA 25.6 weeks, and PNA 29 days, CL
FORMATION KETO-DOXAPRAM
was 0.115 L/h (relative standard error (RSE) 12%) and CL
DOXAPRAM OTHER ROUTES
was 0.645 L/h (RSE 9%). Oral bioavailability was estimated at 74% (RSE 10%).
Conclusions
Dosing of doxapram only based on bodyweight results in the highest exposure in preterm infants with the lowest PNA and GA. Therefore, dosing may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. For switching to oral therapy, a 33% dose increase is required to maintain exposure.
Impact
Current dosing regimens of doxapram in preterm infants only based on bodyweight result in the highest exposure in infants with the lowest PNA and GA.
Dosing of doxapram may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events.
Describing the pharmacokinetics of doxapram and its active metabolite keto-doxapram following intravenous and gastroenteral administration enables to include drug exposure to the evaluation of treatment of AOP.
The oral bioavailability of doxapram in preterm neonates is 74%, requiring a 33% higher dose via oral than intravenous administration to maintain exposure.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/s41390-020-1037-9</identifier><identifier>PMID: 32698193</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Administration, Oral ; Bioavailability ; Body Weight ; Clinical Research Article ; Doxapram - pharmacokinetics ; Female ; Gestational Age ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Newborn, Diseases - drug therapy ; Infant, Premature ; Infant, Premature, Diseases - drug therapy ; Male ; Medicine ; Medicine & Public Health ; Newborn babies ; Nonlinear Dynamics ; Pediatric Surgery ; Pediatrics ; Pharmacokinetics ; Premature babies ; Reproducibility of Results ; Risk ; Sleep Apnea, Central - drug therapy</subject><ispartof>Pediatric research, 2021-04, Vol.89 (5), p.1268-1277</ispartof><rights>International Pediatric Research Foundation, Inc 2020</rights><rights>International Pediatric Research Foundation, Inc 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-57cc96923b0c1ecbe893de100f44bf9d321b95c59dca7b37e5a9de05089333103</citedby><cites>FETCH-LOGICAL-c415t-57cc96923b0c1ecbe893de100f44bf9d321b95c59dca7b37e5a9de05089333103</cites><orcidid>0000-0002-3658-594X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32698193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Flint, Robert B.</creatorcontrib><creatorcontrib>Simons, Sinno H. P.</creatorcontrib><creatorcontrib>Andriessen, Peter</creatorcontrib><creatorcontrib>Liem, Kian D.</creatorcontrib><creatorcontrib>Degraeuwe, Pieter L. J.</creatorcontrib><creatorcontrib>Reiss, Irwin K. M.</creatorcontrib><creatorcontrib>Ter Heine, Rob</creatorcontrib><creatorcontrib>Engbers, Aline G. J.</creatorcontrib><creatorcontrib>Koch, Birgit C. P.</creatorcontrib><creatorcontrib>Groot, Ronald de</creatorcontrib><creatorcontrib>Burger, David M.</creatorcontrib><creatorcontrib>Knibbe, Catherijne A. J.</creatorcontrib><creatorcontrib>Völler, Swantje</creatorcontrib><creatorcontrib>DINO Research Group</creatorcontrib><creatorcontrib>DINO Research Group</creatorcontrib><title>The bioavailability and maturing clearance of doxapram in preterm infants</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background
Doxapram is used for the treatment of apnea of prematurity in dosing regimens only based on bodyweight, as pharmacokinetic data are limited. This study describes the pharmacokinetics of doxapram and keto-doxapram in preterm infants.
Methods
Data (302 samples) from 75 neonates were included with a median (range) gestational age (GA) 25.9 (23.9–29.4) weeks, bodyweight 0.95 (0.48–1.61) kg, and postnatal age (PNA) 17 (1–52) days at the start of continuous treatment. A population pharmacokinetic model was developed using non-linear mixed-effects modelling (NONMEM®).
Results
A two-compartment model best described the pharmacokinetics of doxapram and keto-doxapram. PNA and GA affected the formation clearance of keto-doxapram (CL
FORMATION KETO-DOXAPRAM
) and clearance of doxapram via other routes (CL
DOXAPRAM OTHER ROUTES
). For a median individual of 0.95 kg, GA 25.6 weeks, and PNA 29 days, CL
FORMATION KETO-DOXAPRAM
was 0.115 L/h (relative standard error (RSE) 12%) and CL
DOXAPRAM OTHER ROUTES
was 0.645 L/h (RSE 9%). Oral bioavailability was estimated at 74% (RSE 10%).
Conclusions
Dosing of doxapram only based on bodyweight results in the highest exposure in preterm infants with the lowest PNA and GA. Therefore, dosing may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. For switching to oral therapy, a 33% dose increase is required to maintain exposure.
Impact
Current dosing regimens of doxapram in preterm infants only based on bodyweight result in the highest exposure in infants with the lowest PNA and GA.
Dosing of doxapram may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events.
Describing the pharmacokinetics of doxapram and its active metabolite keto-doxapram following intravenous and gastroenteral administration enables to include drug exposure to the evaluation of treatment of AOP.
The oral bioavailability of doxapram in preterm neonates is 74%, requiring a 33% higher dose via oral than intravenous administration to maintain exposure.</description><subject>Administration, Oral</subject><subject>Bioavailability</subject><subject>Body Weight</subject><subject>Clinical Research Article</subject><subject>Doxapram - pharmacokinetics</subject><subject>Female</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Low Birth Weight</subject><subject>Infant, Newborn</subject><subject>Infant, Newborn, Diseases - drug therapy</subject><subject>Infant, Premature</subject><subject>Infant, Premature, Diseases - drug therapy</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Newborn babies</subject><subject>Nonlinear Dynamics</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Pharmacokinetics</subject><subject>Premature babies</subject><subject>Reproducibility of Results</subject><subject>Risk</subject><subject>Sleep Apnea, Central - drug therapy</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kE1PxCAQhonRuOvqD_BiSDyjUKAtR7PxY5NNvKxnAnSq3fRLaI3-e2m66snTzJBn3gkPQpeM3jDK89sgGFeU0ISSOGdEHaElkzy-CJEdoyWlnBGuVL5AZyHsKWVC5uIULXiSqpwpvkSb3RtgW3Xmw1S1sVVdDV_YtAVuzDD6qn3FrgbjTesAdyUuuk_Te9PgqsW9hwH81JamHcI5OilNHeDiUFfo5eF-t34i2-fHzfpuS5xgciAyc06lKuGWOgbOQq54AYzSUghbqoInzCrppCqcySzPQBpVAJU0cpzHb67Q9Zzb--59hDDofTf6Np7UiUxSkaWS8UixmXK-C8FDqXtfNcZ_aUb1JE_P8nSUN82ZVnHn6pA82gaK340fWxFIZiD0kxrwf6f_T_0GTfB5gg</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Flint, Robert B.</creator><creator>Simons, Sinno H. P.</creator><creator>Andriessen, Peter</creator><creator>Liem, Kian D.</creator><creator>Degraeuwe, Pieter L. J.</creator><creator>Reiss, Irwin K. M.</creator><creator>Ter Heine, Rob</creator><creator>Engbers, Aline G. J.</creator><creator>Koch, Birgit C. P.</creator><creator>Groot, Ronald de</creator><creator>Burger, David M.</creator><creator>Knibbe, Catherijne A. J.</creator><creator>Völler, Swantje</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</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><orcidid>https://orcid.org/0000-0002-3658-594X</orcidid></search><sort><creationdate>20210401</creationdate><title>The bioavailability and maturing clearance of doxapram in preterm infants</title><author>Flint, Robert B. ; Simons, Sinno H. P. ; Andriessen, Peter ; Liem, Kian D. ; Degraeuwe, Pieter L. J. ; Reiss, Irwin K. M. ; Ter Heine, Rob ; Engbers, Aline G. J. ; Koch, Birgit C. P. ; Groot, Ronald de ; Burger, David M. ; Knibbe, Catherijne A. J. ; Völler, Swantje</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-57cc96923b0c1ecbe893de100f44bf9d321b95c59dca7b37e5a9de05089333103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Administration, Oral</topic><topic>Bioavailability</topic><topic>Body Weight</topic><topic>Clinical Research Article</topic><topic>Doxapram - pharmacokinetics</topic><topic>Female</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Low Birth Weight</topic><topic>Infant, Newborn</topic><topic>Infant, Newborn, Diseases - drug therapy</topic><topic>Infant, Premature</topic><topic>Infant, Premature, Diseases - drug therapy</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Newborn babies</topic><topic>Nonlinear Dynamics</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Pharmacokinetics</topic><topic>Premature babies</topic><topic>Reproducibility of Results</topic><topic>Risk</topic><topic>Sleep Apnea, Central - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Flint, Robert B.</creatorcontrib><creatorcontrib>Simons, Sinno H. P.</creatorcontrib><creatorcontrib>Andriessen, Peter</creatorcontrib><creatorcontrib>Liem, Kian D.</creatorcontrib><creatorcontrib>Degraeuwe, Pieter L. J.</creatorcontrib><creatorcontrib>Reiss, Irwin K. M.</creatorcontrib><creatorcontrib>Ter Heine, Rob</creatorcontrib><creatorcontrib>Engbers, Aline G. J.</creatorcontrib><creatorcontrib>Koch, Birgit C. P.</creatorcontrib><creatorcontrib>Groot, Ronald de</creatorcontrib><creatorcontrib>Burger, David M.</creatorcontrib><creatorcontrib>Knibbe, Catherijne A. J.</creatorcontrib><creatorcontrib>Völler, Swantje</creatorcontrib><creatorcontrib>DINO Research Group</creatorcontrib><creatorcontrib>DINO Research Group</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</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>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Flint, Robert B.</au><au>Simons, Sinno H. P.</au><au>Andriessen, Peter</au><au>Liem, Kian D.</au><au>Degraeuwe, Pieter L. J.</au><au>Reiss, Irwin K. M.</au><au>Ter Heine, Rob</au><au>Engbers, Aline G. J.</au><au>Koch, Birgit C. P.</au><au>Groot, Ronald de</au><au>Burger, David M.</au><au>Knibbe, Catherijne A. J.</au><au>Völler, Swantje</au><aucorp>DINO Research Group</aucorp><aucorp>DINO Research Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The bioavailability and maturing clearance of doxapram in preterm infants</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>89</volume><issue>5</issue><spage>1268</spage><epage>1277</epage><pages>1268-1277</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Background
Doxapram is used for the treatment of apnea of prematurity in dosing regimens only based on bodyweight, as pharmacokinetic data are limited. This study describes the pharmacokinetics of doxapram and keto-doxapram in preterm infants.
Methods
Data (302 samples) from 75 neonates were included with a median (range) gestational age (GA) 25.9 (23.9–29.4) weeks, bodyweight 0.95 (0.48–1.61) kg, and postnatal age (PNA) 17 (1–52) days at the start of continuous treatment. A population pharmacokinetic model was developed using non-linear mixed-effects modelling (NONMEM®).
Results
A two-compartment model best described the pharmacokinetics of doxapram and keto-doxapram. PNA and GA affected the formation clearance of keto-doxapram (CL
FORMATION KETO-DOXAPRAM
) and clearance of doxapram via other routes (CL
DOXAPRAM OTHER ROUTES
). For a median individual of 0.95 kg, GA 25.6 weeks, and PNA 29 days, CL
FORMATION KETO-DOXAPRAM
was 0.115 L/h (relative standard error (RSE) 12%) and CL
DOXAPRAM OTHER ROUTES
was 0.645 L/h (RSE 9%). Oral bioavailability was estimated at 74% (RSE 10%).
Conclusions
Dosing of doxapram only based on bodyweight results in the highest exposure in preterm infants with the lowest PNA and GA. Therefore, dosing may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. For switching to oral therapy, a 33% dose increase is required to maintain exposure.
Impact
Current dosing regimens of doxapram in preterm infants only based on bodyweight result in the highest exposure in infants with the lowest PNA and GA.
Dosing of doxapram may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events.
Describing the pharmacokinetics of doxapram and its active metabolite keto-doxapram following intravenous and gastroenteral administration enables to include drug exposure to the evaluation of treatment of AOP.
The oral bioavailability of doxapram in preterm neonates is 74%, requiring a 33% higher dose via oral than intravenous administration to maintain exposure.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>32698193</pmid><doi>10.1038/s41390-020-1037-9</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3658-594X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-3998 |
| ispartof | Pediatric research, 2021-04, Vol.89 (5), p.1268-1277 |
| issn | 0031-3998 1530-0447 |
| language | eng |
| recordid | cdi_proquest_journals_2526476513 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Administration, Oral Bioavailability Body Weight Clinical Research Article Doxapram - pharmacokinetics Female Gestational Age Humans Infant Infant, Low Birth Weight Infant, Newborn Infant, Newborn, Diseases - drug therapy Infant, Premature Infant, Premature, Diseases - drug therapy Male Medicine Medicine & Public Health Newborn babies Nonlinear Dynamics Pediatric Surgery Pediatrics Pharmacokinetics Premature babies Reproducibility of Results Risk Sleep Apnea, Central - drug therapy |
| title | The bioavailability and maturing clearance of doxapram in preterm infants |
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