Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis

Morales-León, Felipe; Plessing-Rossel, Carlos von; Villa‐Zapata, Lorenzo; Fernández-Rocca, Pola; Sanhueza-Sanhueza, Cindy; Bello-Toledo, Helia; Mella-Montecinos, Sergio

doi:10.4067/s0716-10182015000300001

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…In vitro susceptibility studies for MTZ have indicated MIC 90 values below 2 μg/mL for gram‐negative anaerobes and under 4 μg/mL for Clostridium species (Prescott & Baggot, 1988). Additionally, an AUC (0–24 h) /MIC ratio of ≥70 has been recommended for MTZ for optimal efficacy against various anaerobic pathogens (Child et al., 2019; Morales‐León et al., 2015). Considering that the plasma protein binding is assumed to be negligible in geese, the AUC (0–24 h) /MIC ratio surpassed 70 for the oral dose of 50 mg/kg, but fell below 70 for the IV dose of 10 mg/kg, for a MIC value of 4 μg/mL.…”

Section: Discussionmentioning

confidence: 99%

Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations

Fadel,

Łebkowska‐Wieruszewska,

Bourdo

et al. 2023

Vet Pharm & Therapeutics

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Metronidazole (MTZ) is a 5‐nitroimidazole anti‐bacterial and anti‐protozoal drug. In human and companion animal medicine, MTZ remains widely used due to its effectiveness against anaerobic bacteria and protozoa. In farm animals, however, MTZ is currently prohibited in several countries due to insufficient data on nitroimidazoles. The purpose of this study was to assess its pharmacokinetics (PK) in geese after single intravenous (IV) and oral (PO) administrations. Fifteen‐month old healthy male geese (n = 8) were used. Geese were subjected to a two‐phase, single‐dose (10 mg/kg IV, 50 mg/kg PO), open, longitudinal study design with a two‐week washout period between the IV and PO phases. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma MTZ concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software with a non‐compartmental approach. MTZ was still quantifiable and well above the LLOQ at 24 h after both routes of administration. Following IV administration, terminal elimination half‐life, volume of distribution, and total clearance were 5.47 h, 767 mL/kg, and 96 mL/h/kg, respectively. For the PO route, the bioavailability was high (85%), and the mean peak plasma concentration was 60.27 μg/mL at 1 h. When parameters were normalized for the dose, there were no statistically significant differences for any of the PK parameters between the two routes of administration. The study shows that oral administration of MTZ seems to be promising in geese, although comprehensive research on its pharmacodynamics and multiple‐dose studies are necessary before its adoption in geese can be further considered.

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Section: Discussionmentioning

confidence: 99%

Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations

Fadel,

Łebkowska‐Wieruszewska,

Bourdo

et al. 2023

Vet Pharm & Therapeutics

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“…27 Human pharmacokinetic and pharmacodynamic studies have suggested that a once daily systemic administration of metronidazole was possible in some groups of patients. 30,31 It was shown that IVRLP with time dependent antibiotic medication, once a day therapy, can be curative. [32][33][34] The theory behind those cases is that even for time dependant antibiotic medications, a high C max /MIC ratio has a significant positive impact by increasing the kill and decreasing resistance formation.…”

Section: Discussionmentioning

confidence: 99%

The Concentration of Metronidazole in the Distal Interphalangeal Joint following Intravenous Regional Limb Perfusion via the Cephalic Vein in Standing Horses

Gustafsson

Tatz

Dahan

et al. 2021

Vet Comp Orthop Traumatol

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Objective The aim of this study was to determine the concentration of metronidazole in the distal interphalangeal joint (DIPJ) of the thoracic limb after administering metronidazole to standing horses by intravenous regional limb perfusion (IVRLP). Methods Eleven healthy horses had a wide rubber tourniquet applied to the proximal aspect of the antebrachium for 0.5 hours and 500 mg of metronidazole diluted in physiologic saline solution to a total volume of 108 mL was administered by cephalic IVRLP. Synovial fluid samples were collected from the DIPJ before perfusion and at 0.25, 0.5, 2, 12 and 24 hours. Blood samples were obtained at the same time points for serum analysis. Concentrations of metronidazole were determined by liquid chromatography/tandem mass spectrometry. Results Four horses were excluded due to low synovial fluid concentrations and not completing the full tourniquet application time. The C max in the synovial fluid was 327 ± 208 µg/mL, and the t max was 26 ± 7 minutes. Only the concentrations of metronidazole at time points 0.25 and 0.5 hours were significantly different (p < 0.001) from synovial concentration before perfusion. The serum C max was 1.78 ± 0.93 µg/mL, and the t max was 76 ± 52min. Conclusion Metronidazole administered by IVRLP reached high concentrations in the synovial fluid at 0.5 hours. However, the concentrations rapidly decreased below the minimum inhibitory concentration of potential target pathogens. Effectiveness of metronidazole administered by IVRLP as a sole therapy against anaerobic infections of synovial structures of the distal limb cannot be determined by a pharmacokinetic study. However, the present study serves as the basis for future carefully planned clinical trials.

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“…Giardia is virtually never invasive, 24 so one idea for an effective therapy would require delivery of the drug to the lumen of the intestinal tract. However, this is not the only method, considering metronidazole has outstanding oral bioavailability, 25 with a concentration in the small intestine that is similar to the plasma level. It is probably largely delivered to the Giardia cells in the small intestine by secretion from the bloodstream.…”

Section: ■ Introductionmentioning

confidence: 99%

A Curious Case for Development of Kinase Inhibitors as Antigiardiasis Treatments Using Advanced Drug Techniques

et al. 2021

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Giardiasis is a neglected parasitic diarrheal disease that is particularly associated with poverty. Current treatment options are limited in the face of growing resistance, but the reduced kinome of Giardia lamblia increases the likelihood of identifying nonredundant essential kinases as potential drug targets. Repurposing known and newly identified kinase inhibitors in drug development programs for novel giardiasis therapeutics could therefore be a cost-effective and time saving approach. Innovative improvements to physiologically-based pharmacokinetic modeling coupled with emerging imaging technologies and a CRISPRinterference method could accelerate progress toward the goal of more effective giardiasis therapeutics based on kinase inhibition.

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Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis

Cited by 4 publications

References 24 publications

Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations

Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations

The Concentration of Metronidazole in the Distal Interphalangeal Joint following Intravenous Regional Limb Perfusion via the Cephalic Vein in Standing Horses

A Curious Case for Development of Kinase Inhibitors as Antigiardiasis Treatments Using Advanced Drug Techniques

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