Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Antimicrob Agents Chemother ; 67(12): e0096223, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-37971244

RESUMO

Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration. The safety, tolerability, and pharmacokinetics of subcutaneous infusions of high-dose BPG were assessed in 24 healthy adult volunteers assigned to receive either 3.6, 7.2, or 10.8 MU (three, six, and nine times the standard dose, respectively) as a single subcutaneous infusion. The delivery of the BPG to the subcutaneous tissue was confirmed with ultrasonography. Safety assessments, pain scores, and penicillin concentrations were measured for 16 weeks post-dose. Subcutaneous infusion of penicillin (SCIP) was generally well tolerated with all participants experiencing transient, mild infusion-site reactions. Prolonged elevated penicillin concentrations were described using a combined zero-order (44 days) and first-order (t1/2 = 12 days) absorption pharmacokinetic model. In simulations, time above the conventionally accepted target concentration of 20 ng/mL (0.02 µg/mL) was 57 days for 10.8 MU delivered by subcutaneous infusion every 13 weeks compared with 9 days of every 4-weekly dosing interval for the standard 1.2 MU intramuscular dose (i.e., 63% and 32% of the dosing interval, respectively). High-dose SCIP (BPG) is safe, has acceptable tolerability, and may be suitable for up to 3 monthly dosing intervals for secondary prophylaxis of RHD.


Assuntos
Febre Reumática , Cardiopatia Reumática , Adulto , Humanos , Antibacterianos/farmacocinética , Infusões Subcutâneas , Dor/tratamento farmacológico , Penicilina G Benzatina/efeitos adversos , Febre Reumática/prevenção & controle , Cardiopatia Reumática/tratamento farmacológico , Cardiopatia Reumática/prevenção & controle
2.
Pharmacol Res Perspect ; 8(6): e00668, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33090729

RESUMO

Benzathine penicillin G (BPG) is used as first-line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web-based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty-five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 µm) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG.


Assuntos
Antibacterianos/normas , Química Farmacêutica/normas , Internacionalidade , Penicilina G Benzatina/normas , Controle de Qualidade , Antibacterianos/uso terapêutico , Química Farmacêutica/métodos , Estudos Transversais , Humanos , Penicilina G Benzatina/uso terapêutico , Cardiopatia Reumática/tratamento farmacológico
4.
J Antimicrob Chemother ; 74(7): 1984-1991, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30989171

RESUMO

BACKGROUND: Benzathine benzylpenicillin G (BPG) is recommended as secondary prophylaxis to prevent recurrence of acute rheumatic fever and subsequent rheumatic heart disease (RHD). Following intramuscular injection, BPG is hydrolysed to benzylpenicillin. Little is known of the pharmacokinetics of benzylpenicillin following BPG in populations at risk of RHD. METHODS: We conducted a longitudinal pharmacokinetic study of children and adolescents receiving secondary prophylaxis throughout six monthly cycles of BPG. Dried blood spot samples were assayed with LC-MS/MS. Benzylpenicillin concentrations were analysed using non-linear mixed-effects modelling with subsequent simulations based on published BMI-for-age and weight-for-age data. RESULTS: Eighteen participants contributed 256 concentrations for analysis. None had benzylpenicillin concentrations >0.02 mg/L for the full time between doses. The median duration above this target was 9.8 days for those with a lower BMI (<25 kg/m2), who also had lower weights, and 0 days for those with a higher BMI (≥25 kg/m2). Although fat-free mass was a key determinant of benzylpenicillin exposure after a standard dose of BPG, having a higher BMI influenced absorption and almost doubled (increase of 86%) the observed t½. CONCLUSIONS: Few children and adolescents receiving BPG as secondary prophylaxis will achieve concentrations >0.02 mg/L for the majority of the time between injections. The discordance of this observation with reported efficacy of BPG to prevent rheumatic fever implies a major knowledge gap relating to pharmacokinetic/pharmacodynamic relationships between benzylpenicillin exposure and clinical outcomes.


Assuntos
Antibacterianos/farmacocinética , Infecções Bacterianas/complicações , Penicilina G Benzatina/farmacocinética , Febre Reumática/etiologia , Febre Reumática/prevenção & controle , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/prevenção & controle , Adolescente , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Biomarcadores , Criança , Feminino , Humanos , Masculino , Modelos Teóricos , Penicilina G Benzatina/administração & dosagem , Febre Reumática/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...