MULTIPLE DOSE PHARMACOKINETIC STUDY OF MEROPENEM IN YOUNG INFANTS (91 DAYS)

美罗培南多剂量小婴儿药代动力学研究（91天）

• 批准号: 8167326
• 负责人: JOHANNES NICOLAAS VAN DEN ANKER
• 金额: $ 0.1万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-20 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167326
• 关键词: Abdominal Infection; Adolescence; Adult; Age-Months; AmpC beta-lactamases; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Meningitis; Carbapenems; Childhood; Computer Retrieval of Information on Scientific Projects Database; Data; Dose; Drug Kinetics; Excretory function; Funding; Grant; Half-Life; Hour; Hydrolysis; Infant; Infection; Institution; Intra-abdominal; Intravenous; Label; Life; Meropenem; Metabolism; Multi-Drug Resistance; Penicillin Resistance; Plasma; Plasma Proteins; Protein Binding; Pseudomonas aeruginosa; Regimen; Renal function; Research; Research Personnel; Resources; Safety; Sepsis; Source; Streptococcus pneumoniae; United States National Institutes of Health; Urine; antimicrobial; antimicrobial drug; beta-Lactamase; neonate; pathogen; urinary; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Meropenem, a carbapenem, belongs to an antibiotic class that possesses one of the broadest spectra of antimicrobial activity available, including most of the bacterial pathogens responsible for serious, life-threatening infections occurring in young (91 days) infants. Meropenem is stable against hydrolysis by most extended spectrum beta-lactamases and AmpC chromosomal beta-lactamases underscoring the drug¿¿"s activity against many antibiotic resistant Gram positive (e.g., penicillin-resistant S. pneumoniae) and Gram negative (e.g., P. aeruginosa) bacteria. Important indications for meropenem involve infections due to multi-drug resistant pathogens and polymicrobial sepsis. Meropenem is FDA-labeled for pediatric subjects from three months of age through adolescence as single agent antimicrobial therapy for bacterial meningitis and complicated intra-abdominal infections. There is substantial off-label use of meropenem in neonates and infants younger than three months of age. This off-label use occurs despite the lack of adequate meropenem pharmacokinetic, dosing, tolerability and safety data for this vulnerable subject group. The present proposal aims to determine pharmacokinetics and safety of meropenem for the treatment of suspected and complicated intra-abdominal infection in neonates and infants younger than three months of age. Metabolism in Adults: Meropenem mean peak plasma concentrations were approximately 23 ¿¿g/mL (range 14-26) for 500 mg single dose and 49 ¿¿g/mL (range 39-58) for a 1 g single dose in adult volunteers,. Following intravenous doses of 500 mg in adults mean plasma concentrations of meropenem usually decline to approximately 1 ¿¿g/mL at 6 hours after administration. In subjects with normal renal function, the elimination half-life of meropenem is approximately 1 hour. Approximately 70% of the intravenously administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Urinary concentrations of meropenem in excess of 10 ¿¿g/mL are maintained for up to 5 hours after a 500 mg dose. No accumulation of meropenem in plasma or urine was observed with regimens using 500 mg administered every 8 hours or 1 g administered every 6 hours in volunteers with normal renal function. Plasma protein binding of meropenem is approximately 2%. There is one metabolite which is microbiologically inactive.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 Meropenem是一种碳青霉烯，属于一种抗生素类别，该类别具有可用的抗菌活性最广泛的谱之一，包括大多数造成严重，威胁生命的感染的细菌病原体，发生在年轻（91天）的婴儿中。 Meropenem对大多数扩展的光谱β-内酰胺酶和AMPC染色体β-内酰胺酶的水解稳定，这强调了药物对许多抗生素耐药的活性，例如，抗药性抗生素持续的呈阳性（例如，耐药性S.肺炎S.肺炎）和革脉含量（例如，p. p. p. p. p. p. p. p. p. p. p. p. p. aeruginosa））多毒病原体和多型败血症。该脆弱的受试者缺乏足够的Meropenem药代动力学，剂量，耐受性和安全性数据。成人的代谢：MeropeNEM平均峰血浆浓度约为23€g/ml（范围14-26），单剂量为500 mg，而成人志愿者1 g单剂量的单剂量为49毫升（范围39-58）。在静脉注射剂量后，成年人的静脉剂量为500 mg，平均血浆浓度在给药后6小时时通常下降至大约1'g/ml。在具有正常肾功能的受试者中，MeropeNem的消除半衰期约为1小时。在12小时内，静脉内施用的剂量中约有70％被回收为尿液中未改变的梅罗皮纳姆，此后几乎几乎没有进一步的尿液极端。在500 mg剂量后，将尿中的美培香气的尿液浓度超过10»g/ml。使用500 mg的肾功能志愿者每6小时服用500 mg，在血浆或尿液中未观察到Meropemenem或尿液的积累。 Meropenem的血浆蛋白结合约为2％。有一种代谢物在微生物学上无活性。