Supporting Development of a New Antibacterial Drug

In recent years, proliferation of plasmids encoding extended-spectrum β-lactamases (ESBLs) has fueled the rise of multi-drug resistant Gram-negative bacterial infections. Avibactam inhibits class A and C serine β-lactamases, including KPC carbapenemases. While avibactam itself is not bactericidal, it restores the effectiveness of β-lactam antibiotics, including ceftazidime, against ESBL-producing pathogens. The sponsor sought to combine avibactam […]

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Month 2 culture status and treatment duration as predictors of recurrence in pulmonary tuberculosis: model validation and update.

New regimens capable of shortening tuberculosis treatment without increasing the risk of recurrence are urgently needed. A 2013 meta-regression analysis, using data from trials published from 1973 to 1997 involving 7793 patients, identified 2-month sputum culture status and treatment duration as independent predictors of recurrence. The resulting model predicted that if a new 4-month regimen […]

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Safety and pharmacokinetics of single and multiple ascending doses of avibactam alone and in combination with ceftazidime in healthy male volunteers: results of two randomized, placebo-controlled studies.

Avibactam is a novel non-β-lactam β-lactamase inhibitor effective against Ambler class A, C and some class D β-lactamases that is currently in clinical development in combination with ceftazidime for the treatment of serious Gram-negative infections. It restores the in vitro activity of a range of β-lactams, including ceftazidime, against extended-spectrum β-lactamase-producing pathogens. Two phase I […]

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Effect of age and sex on the pharmacokinetics and safety of avibactam in healthy volunteers

Avibactam is a novel non-β-lactam β-lactamase inhibitor currently being assessed in combination with ceftazidime, ceftaroline fosamil, and aztreonam. The objectives of this study were to investigate the pharmacokinetics, safety, and tolerability of avibactam in healthy young (aged 18-45 years) and elderly (aged ≥65 years) volunteers of both sexes. This was a Phase I, open-label study […]

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Phase 1 Study Assessing the Pharmacokinetic Profile and Safety of Avibactam in Patients with Renal Impairment.

Avibactam is a non-β-lactam β-lactamase inhibitor intended for use as a fixed-dose combination with ceftazidime for the treatment of certain serious Gram-negative infections. As avibactam is primarily excreted unchanged in the urine, renal impairment may affect its pharmacokinetics. This Phase 1 study investigated the effect of renal impairment and hemodialysis on avibactam pharmacokinetics and safety. […]

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Getting at the HAART of Precision Dosing: Using PBPK Models to Optimize Dosing of an Antiviral

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1. It is primarily metabolized by CY2B6. A standard dose of efavirenz has been associated with serious adverse reactions in poor metabolizers (PMs) of CYP2B6, necessitating a reduction […]

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Physiologically-based Modeling Supports Drug Development Decisions, Regulatory Interactions and Drug Labeling

Today’s powerful and actively evolving computational tools enable sponsors and regulators to understand potential drug characteristics and subject responses earlier in development, with greater certainty. Model-based approaches support timely, confident decisions across the development and regulatory life cycle by gathering disparate sources of information about a drug, its competitors, target disease and patients into a […]

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Modeling the Influence of Ethnicity on Drug Disposition

Physiologically-based pharmacokinetic (PBPK) modeling and simulation in virtual populations can uncover changes in drug disposition due to ethnic differences, providing supporting information for regulatory review and helping identify and optimize essential bridging studies. Ethnic diversity in drug response and its impact on dosing has been well described for some drugs. A recent study of the most […]

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Assessing the impact of liver or kidney disease on pharmacokinetics

Major pharmaceutical companies and drug regulatory agencies are using physiologically-based pharmacokinetic (PBPK) modeling in virtual populations to investigate the impact of hepatic or renal impairment on drug exposure as a supplement to clinical investigation and help guide dosage adjustment in these patient groups Impaired hepatic or renal function can have a major impact on pharmacokinetics […]

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Getting a Novel Antibiotic to Patients

From pre-clinical toxicokinetics to final dose recommendations, Certara helped Cubist Pharmaceuticals obtain regulatory approval of a new treatment for complicated infections. At least two million people become infected with treatment-resistant bacteria each year in the US alone. At least 23,000 die as a direct result; many more lose their lives to other conditions complicated by […]

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