The clinical pharmacokinetics of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate

Kaye, C M; Allen, Ann; Perry, Sheryl; McDonagh, Margaret; Davy, Maria; Storm, Kevin G.; Bird, Nicholas; Dewit, Odile

doi:10.1016/s0149-2918(01)80061-8

Cited by 79 publications

(72 citation statements)

References 5 publications

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“…Human target profiles were based on those published in the literature (4, 9, 13, 18). (4,9,13,18). b C is the concentration in plasma at time t, A is the zero-time intercept assuming instantaneous absorption, e is the base of the natural log, k el is the elimination constant, and k a is the absorption rate constant.…”

Section: Methodsmentioning

confidence: 99%

“…The 2,000/125 mg twice a day (ratio 16:1) regimen of amoxicillin-clavulanate has been designed with a sustained-release amoxicillin component to give a specific pharmacokinetic profile in humans following oral dosing (18). Concentrations for this novel formulation were determined from the addition of two individual one-compartment absorption models.…”

Section: Vol 49 2005 Efficacy Of Enhanced Amoxicillin-clavulanate 909mentioning

confidence: 99%

“…Levofloxacin was assayed with a commercially available Bacillus subtilis NCTC 6633 spore suspension (Difco) in nutrient agar (BBL). Potassium clavulanate was assayed by an enzyme inhibition assay with Klebsiella pneumoniae NCTC 11228 in nutrient agar supplemented with 60 g of benzylpenicillin per ml (18).…”

Section: Vol 49 2005 Efficacy Of Enhanced Amoxicillin-clavulanate 909mentioning

confidence: 99%

“…This formulation is given as two tablets, each of which consists of a bilayer comprising a sustained-release layer of sodium amoxicillin (437.5 mg) and an immediate-release layer of amoxicillin trihydrate (562.5 mg)/ potassium clavulanate (62.5 mg). This bilayer design extends the duration of the dosing interval for which serum amoxicillin concentrations are above the MIC to 49% for strains with MICs of 4 g/ml and 35% for strains with MICs of 8 g/ml (18).…”

mentioning

confidence: 99%

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Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against Streptococcus pneumoniae with Elevated Amoxicillin MICs and Haemophilus influenzae

Berry

Hoover

Singley

et al. 2005

Antimicrob Agents Chemother

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A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate (2,000 mg of amoxicillin/125 mg of clavulanate twice a day; ratio 16:1) has been designed, with sustained-release technology, to allow coverage of bacterial strains with amoxicillin-clavulanic acid MICs of at least 4/2 g/ml. The bacteriological efficacy of amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was compared in a rat model of respiratory tract infection versus four other amoxicillin-clavulanate formulations: 8:1 three times a day (1,000/125 mg), 7:1 three times a day (875/125 mg), 7:1 twice a day (875/125 mg), and 4:1 three times a day (500/125 mg); levofloxacin (500 mg once a day); and azithromycin (1,000 mg on day 1 followed thereafter by 500 mg once a day). Bacterial strains included Streptococcus pneumoniae, with amoxicillin-clavulanic acid MICs of 2/1 (one strain), 4/2, or 8/4 g/ml (three strains each), and Haemophilus influenzae, one ␤-lactamase-positive strain and one ␤-lactamasenegative, ampicillin-resistant strain. Animals were infected by intrabronchial instillation. Antibacterial treatment commenced 24 h postinfection, with doses delivered by computer-controlled intravenous infusion to approximate the concentrations achieved in human plasma following oral administration. Plasma concentrations in the rat corresponded closely with target human concentrations for all antimicrobials tested. Amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was effective against all S. pneumoniae strains tested, including those with amoxicillin-clavulanic acid MICs of up to 8/4 g/ml and against ␤-lactamase-producing and ␤-lactamase-negative ampicillin-resistant H. influenzae. These results demonstrate the bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate 2,000/125 mg twice a day (ratio 16:1) against S. pneumoniae with amoxicillin-clavulanic acid MICs of at least 4/2 g/ml and support clavulanate 125 mg twice a day as sufficient to protect against ␤-lactamase in this rat model.Antimicrobial agent-resistant strains of the key respiratory tract pathogens are widespread, and their prevalence is increasing in many areas (12,15). For Haemophilus influenzae collected in the Alexander Project in 2001, the prevalence of ␤-lactamase production exceeded 24% in the United States and was more than 10% in 9 of the 16 countries included within the study (27). In the same study, the prevalence of penicillin-resistant Streptococcus pneumoniae in 2001 was approximately 20% in the United States and over 30% in Spain, Japan, France, and Hong Kong. The prevalence of macrolideresistant S. pneumoniae was also high in the United States (28%) and was at least 10% in 12 of the 16 countries included within the study (27). Data from the 1998 to 2000 Alexander Project and other surveillance studies have reported similar findings (15)(16)(17)26).Amoxicillin-clavulanate is a combination of the ␤-lactam antibiotic amoxicillin and the ␤-lactamase inhibitor clavulanic acid in the potassium form. Clavulanic acid protect...

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Section: Methodsmentioning

confidence: 99%

Section: Vol 49 2005 Efficacy Of Enhanced Amoxicillin-clavulanate 909mentioning

confidence: 99%

Section: Vol 49 2005 Efficacy Of Enhanced Amoxicillin-clavulanate 909mentioning

confidence: 99%

mentioning

confidence: 99%

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Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against Streptococcus pneumoniae with Elevated Amoxicillin MICs and Haemophilus influenzae

Berry

Hoover

Singley

et al. 2005

Antimicrob Agents Chemother

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“…Por ejemplo, el abordaje terapéutico de una neumonía extrahospitalaria en la República Checa podría ser diferente al de España, si se tiene en cuenta que en el primero la CIM 90 de neumococo a penicilina es menor o igual a 0,06 mg/l (0% de resistencia a penicilina) y la prevalencia de resistencia a macrólidos es de un 2,2% 73 , situación completamente distinta de la de nuestro país, donde la CIM 90 de penicilina y amoxicilina es de 2 mg/l y la prevalencia de resistencia a macrólidos se sitúa en torno al 35% 2 . En este sentido, se ha diseñado una nueva formulación mejorada farmacocinéticamente de amoxicilina-ácido clavulánico (2.000/125 mg liberación prolongada) que administrada dos veces al día permite erradicar cepas de S. pneumoniae resistentes a penicilina y amoxicilina con CIM de 4 e incluso de 8 mg/l [74][75][76][77][78] , lo que le convierte en el betalactámico oral con mayor cobertura frente al neumococo, y por lo tanto en una futura opción para el tratamiento de infecciones respiratorias de probable etiología neumocócica en áreas con alta prevalencia de resistencia a penicilina y macrólidos, como es el caso de nuestro medio, especialmente si se quiere mantener bajo control el consumo de fluoroquinolonas 23,58 . Datos procedentes de 9 ensayos clínicos mostraron una tasa de erradicación del 98,2% (55/56) en pacientes infectados por neumococo resistente a penicilina (CIM Ն 2 mg/l), incluyendo el 95,2% (20/21) de los casos producidos por neumococo resistente a amoxicilina (CIM de 4 y 8 mg/l) 75 .…”

Section: Herramientas Para Predecir Eficacia: Farmacodinamiaunclassified

Resistencias bacterianas y farmacodinámica como bases de la prescripción de antibióticos en infecciones respiratorias

Aguado-García

Martín-Herrero²,

Lumbreras³

2004

Enferm Infecc Microbiol Clin

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Controlling Drug Release in Oral Product Development Programs: An Industrial Perspective

Martini

Crowley

2011

Controlled Release in Oral Drug Delivery

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Most new drugs for oral administration are released rapidly from the dosage form. This may give "peak-trough" plasma profiles not suited to the drug's mode of action or side effect profile. Traditionally, there were few options for better design to optimize rate or time of release. However, advances in many areas of drug evaluation are now identifying opportunities to modify drug release during earlier phases of development to optimize therapeutic efficacy and reduce undesirable effects. It should also result in better success rates in drug development programs as well as better medications for patient treatment.This chapter explores possibilities for modifying release during Preclinical, Phase 1, Phase 2, and Phase 3 programs. Opportunities to improve performance or find new indications for mature drugs, by controlling release continue to emerge. Such possibilities are also considered. The chapter is written, not only for the product design (formulation) specialist but also for scientists involved in all aspects of drug evaluation and development. Consequently, its focus is on the breadth rather than depth of the topic. Other chapters provide more comprehensive accounts of specific approaches, technologies, and modes of evaluation.

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The clinical pharmacokinetics of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate

Cited by 79 publications

References 5 publications

Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against Streptococcus pneumoniae with Elevated Amoxicillin MICs and Haemophilus influenzae

Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against Streptococcus pneumoniae with Elevated Amoxicillin MICs and Haemophilus influenzae

Resistencias bacterianas y farmacodinámica como bases de la prescripción de antibióticos en infecciones respiratorias

Controlling Drug Release in Oral Product Development Programs: An Industrial Perspective

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