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). Uncer-tainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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PUBLIC LIBRARY SCIENCE
2021
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| Online Access: | http://hdl.handle.net/20.500.11937/88949 |
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| author | Ketema, E.B. Gishen, N.Z. Hailu, A. Leul, A. Hadgu, A. Hagos, K. Berhane, S. Tsega, T. Page-Sharp, Madhu Davis, T.M.E. Moore, Brioni Batty, Kevin Carapetis, J. Salman, S. Manning, L. |
| author_facet | Ketema, E.B. Gishen, N.Z. Hailu, A. Leul, A. Hadgu, A. Hagos, K. Berhane, S. Tsega, T. Page-Sharp, Madhu Davis, T.M.E. Moore, Brioni Batty, Kevin Carapetis, J. Salman, S. Manning, L. |
| author_sort | Ketema, E.B. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| 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). Uncer-tainties 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 outpa-tient clinics. Serum samples were collected weekly for one month after injection and assayed with a liquid chromatography-mass spectroscopy assay. Concentration-time data-sets 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 consider-ations for ARF/RHD control programs. |
| first_indexed | 2025-11-14T11:30:13Z |
| format | Journal Article |
| id | curtin-20.500.11937-88949 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:30:13Z |
| publishDate | 2021 |
| publisher | PUBLIC LIBRARY SCIENCE |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-889492022-08-05T07:20:34Z High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin g injections in ethiopian children and adults with rheumatic heart disease Ketema, E.B. Gishen, N.Z. Hailu, A. Leul, A. Hadgu, A. Hagos, K. Berhane, S. Tsega, T. Page-Sharp, Madhu Davis, T.M.E. Moore, Brioni Batty, Kevin Carapetis, J. Salman, S. Manning, L. Science & Technology Life Sciences & Biomedicine Infectious Diseases Parasitology Tropical Medicine PROPHYLAXIS FEVER POPULATION ECHOCARDIOGRAPHY STREPTOCOCCI PREVENTION PREVALENCE PATTERN Introduction: Intramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncer-tainties 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 outpa-tient clinics. Serum samples were collected weekly for one month after injection and assayed with a liquid chromatography-mass spectroscopy assay. Concentration-time data-sets 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 consider-ations for ARF/RHD control programs. 2021 Journal Article http://hdl.handle.net/20.500.11937/88949 10.1371/journal.pntd.0009399 English http://creativecommons.org/licenses/by/4.0/ PUBLIC LIBRARY SCIENCE fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Infectious Diseases Parasitology Tropical Medicine PROPHYLAXIS FEVER POPULATION ECHOCARDIOGRAPHY STREPTOCOCCI PREVENTION PREVALENCE PATTERN Ketema, E.B. Gishen, N.Z. Hailu, A. Leul, A. Hadgu, A. Hagos, K. Berhane, S. Tsega, T. Page-Sharp, Madhu Davis, T.M.E. Moore, Brioni Batty, Kevin Carapetis, J. Salman, S. Manning, L. High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin g injections in ethiopian children and adults with rheumatic heart disease |
| 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_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_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_sort | high risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin g injections in ethiopian children and adults with rheumatic heart disease |
| topic | Science & Technology Life Sciences & Biomedicine Infectious Diseases Parasitology Tropical Medicine PROPHYLAXIS FEVER POPULATION ECHOCARDIOGRAPHY STREPTOCOCCI PREVENTION PREVALENCE PATTERN |
| url | http://hdl.handle.net/20.500.11937/88949 |