High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease.
Introduction Intramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncertainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection are...
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ftdoajarticles:oai:doaj.org/article:a8be4e16c1974b01be6d3c664dcb0d1a 2023-05-15T15:13:26+02:00 High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease. Ezra B Ketema Nigus Z Gishen Abraha Hailu Abadi Leul Abera Hadgu Kiflom Hagos Samual Berhane Temesgen Tsega Madhu Page-Sharp Timothy Me Davis Brioni Moore Kevin T Batty Jonathan Carapetis Sam Salman Laurens Manning 2021-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009399 https://doaj.org/article/a8be4e16c1974b01be6d3c664dcb0d1a EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009399 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009399 https://doaj.org/article/a8be4e16c1974b01be6d3c664dcb0d1a PLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009399 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009399 2022-12-31T10:48:55Z Introduction Intramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncertainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection are key knowledge gaps for RHD control. Methods To evaluate BPG pharmacokinetics (PK) in patients receiving 4-weekly doses in Ethiopia, we conducted a prospective cohort study of ARF/RHD patients attending cardiology outpatient clinics. Serum samples were collected weekly for one month after injection and assayed with a liquid chromatography-mass spectroscopy assay. Concentration-time datasets for BPG were analyzed by nonlinear mixed effects modelling using NONMEM. Results A total of 190 penicillin concentration samples from 74 patients were included in the final PK model. The median age, weight, BMI was 21 years, 47 kg and 18 kg/m2, respectively. When compared with estimates derived from Indigenous Australian patients, the estimate for median (95% confidence interval) volume of distribution (V/F) was lower (54.8 [43.9-66.3] l.70kg-1) whilst the absorption half-life (t1/2-abs2) was longer (12.0 [8.75-17.7] days). The median (IQR) percentage of time where the concentrations remained above 20 ng/mL and 10 ng/mL within the 28-day treatment cycle was 42.5% (27.5-60) and 73% (58.5-99), respectively. Conclusions The majority of Ethiopian patients receiving BPG as secondary prophylaxis to prevent RHD do not attain target concentrations for more than two weeks during each 4-weekly injection cycle, highlighting the limitations of current BPG strategies. Between-population variation, together with PK differences between different preparations may be important considerations for ARF/RHD control programs. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 6 e0009399 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ezra B Ketema Nigus Z Gishen Abraha Hailu Abadi Leul Abera Hadgu Kiflom Hagos Samual Berhane Temesgen Tsega Madhu Page-Sharp Timothy Me Davis Brioni Moore Kevin T Batty Jonathan Carapetis Sam Salman Laurens Manning High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Introduction Intramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncertainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection are key knowledge gaps for RHD control. Methods To evaluate BPG pharmacokinetics (PK) in patients receiving 4-weekly doses in Ethiopia, we conducted a prospective cohort study of ARF/RHD patients attending cardiology outpatient clinics. Serum samples were collected weekly for one month after injection and assayed with a liquid chromatography-mass spectroscopy assay. Concentration-time datasets for BPG were analyzed by nonlinear mixed effects modelling using NONMEM. Results A total of 190 penicillin concentration samples from 74 patients were included in the final PK model. The median age, weight, BMI was 21 years, 47 kg and 18 kg/m2, respectively. When compared with estimates derived from Indigenous Australian patients, the estimate for median (95% confidence interval) volume of distribution (V/F) was lower (54.8 [43.9-66.3] l.70kg-1) whilst the absorption half-life (t1/2-abs2) was longer (12.0 [8.75-17.7] days). The median (IQR) percentage of time where the concentrations remained above 20 ng/mL and 10 ng/mL within the 28-day treatment cycle was 42.5% (27.5-60) and 73% (58.5-99), respectively. Conclusions The majority of Ethiopian patients receiving BPG as secondary prophylaxis to prevent RHD do not attain target concentrations for more than two weeks during each 4-weekly injection cycle, highlighting the limitations of current BPG strategies. Between-population variation, together with PK differences between different preparations may be important considerations for ARF/RHD control programs. |
format |
Article in Journal/Newspaper |
author |
Ezra B Ketema Nigus Z Gishen Abraha Hailu Abadi Leul Abera Hadgu Kiflom Hagos Samual Berhane Temesgen Tsega Madhu Page-Sharp Timothy Me Davis Brioni Moore Kevin T Batty Jonathan Carapetis Sam Salman Laurens Manning |
author_facet |
Ezra B Ketema Nigus Z Gishen Abraha Hailu Abadi Leul Abera Hadgu Kiflom Hagos Samual Berhane Temesgen Tsega Madhu Page-Sharp Timothy Me Davis Brioni Moore Kevin T Batty Jonathan Carapetis Sam Salman Laurens Manning |
author_sort |
Ezra B Ketema |
title |
High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease. |
title_short |
High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease. |
title_full |
High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease. |
title_fullStr |
High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease. |
title_full_unstemmed |
High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease. |
title_sort |
high risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin g injections in ethiopian children and adults with rheumatic heart disease. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009399 https://doaj.org/article/a8be4e16c1974b01be6d3c664dcb0d1a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009399 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009399 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009399 https://doaj.org/article/a8be4e16c1974b01be6d3c664dcb0d1a |
op_doi |
https://doi.org/10.1371/journal.pntd.0009399 |
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PLOS Neglected Tropical Diseases |
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15 |
container_issue |
6 |
container_start_page |
e0009399 |
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1766343985017651200 |