Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever

© 2017 American Society for Microbiology. All Rights Reserved. Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever...

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Main Authors: Page-Sharp, Madhu, Coward, J., Moore, Brioni, Salman, S., Marshall, L., Davis, T., Batty, Kevin, Manning, L.
Format: Journal Article
Published: American Society for Microbiology 2017
Online Access:http://hdl.handle.net/20.500.11937/56374
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author Page-Sharp, Madhu
Coward, J.
Moore, Brioni
Salman, S.
Marshall, L.
Davis, T.
Batty, Kevin
Manning, L.
author_facet Page-Sharp, Madhu
Coward, J.
Moore, Brioni
Salman, S.
Marshall, L.
Davis, T.
Batty, Kevin
Manning, L.
author_sort Page-Sharp, Madhu
building Curtin Institutional Repository
collection Online Access
description © 2017 American Society for Microbiology. All Rights Reserved. Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and 1 month at 20°C . Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD.
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publishDate 2017
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spelling curtin-20.500.11937-563742023-02-22T06:24:16Z Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever Page-Sharp, Madhu Coward, J. Moore, Brioni Salman, S. Marshall, L. Davis, T. Batty, Kevin Manning, L. © 2017 American Society for Microbiology. All Rights Reserved. Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and 1 month at 20°C . Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD. 2017 Journal Article http://hdl.handle.net/20.500.11937/56374 10.1128/AAC.00252-17 American Society for Microbiology unknown
spellingShingle Page-Sharp, Madhu
Coward, J.
Moore, Brioni
Salman, S.
Marshall, L.
Davis, T.
Batty, Kevin
Manning, L.
Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever
title Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever
title_full Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever
title_fullStr Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever
title_full_unstemmed Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever
title_short Penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin G and other penicillin preparations to prevent rheumatic fever
title_sort penicillin dried blood spot assay for use in patients receiving intramuscular benzathine penicillin g and other penicillin preparations to prevent rheumatic fever
url http://hdl.handle.net/20.500.11937/56374