Effects of housing environment on oral absorption of acetaminophen in healthy Beagles

Madsen, Melanie; Enomoto, Hiroko; Messenger, Kristen M.; Papich, Mark G.

doi:10.2460/ajvr.21.06.0075

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…Within the preclinical investigation under fasted-state conditions, paracetamol and ibuprofen exhibited rapid absorption (Figures and ). In the paracetamol canine PBPK model, the adjusted GTT value fell within physiologically observed GE half-life and T max reports. − In this context, it should be noted that the adjusted GTT value represents the formulation’s GTT, rather than a general GE time for clear fluid. Under fasted conditions, the application of HCl/KCl pretreatment appeared not to affect paracetamol performance or GE substantially in the present study; no effects were expected based on paracetamol’s high solubility and the drug’s ionization properties.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of the Beagle Model in the Evaluation of Paracetamol and Ibuprofen Exposure after Oral Administration to Pediatric Populations: An Exploratory Study

et al. 2023

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The present study aimed to explore the usefulness of beagle dogs in combination with physiologically based pharmacokinetic (PBPK) modeling in the evaluation of drug exposure after oral administration to pediatric populations at an early stage of pharmaceutical product development. An exploratory, single-dose, crossover bioavailability study in six beagles was performed. A paracetamol suspension and an ibuprofen suspension were coadministered in the fasted-state conditions, under reference-meal fed-state conditions, and under infant-formula fedstate conditions. PBPK models developed with GastroPlus v9.7 were used to inform the extrapolation of beagle data to human infants and children. Beagle-based simulation outcomes were compared with published human-adult-based simulations. For paracetamol, fasted-state conditions and reference-meal fed-state conditions in beagles appeared to provide adequate information for the applied scaling approach. Fasted-state and/or reference-meal fed-state conditions in beagles appeared suitable to simulate the performance of ibuprofen suspension in pediatric populations. Contrary to human-adult-based translations, extrapolations based on beagle data collected under infant-formula fed-state conditions appeared less useful for informing simulations of plasma levels in pediatric populations. Beagle data collected under fasted and/or reference-meal fed-state conditions appeared to be useful in the investigation of pediatric product performance of the two investigated highly permeable and highly soluble drugs in the upper small intestine. The suitability of the beagle as a preclinical model to understand pediatric drug product performance under different dosing conditions deserves further evaluation with a broader spectrum of drugs and drug products and comparisons with pediatric in vivo data.

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Section: Discussionmentioning

confidence: 99%

Usefulness of the Beagle Model in the Evaluation of Paracetamol and Ibuprofen Exposure after Oral Administration to Pediatric Populations: An Exploratory Study

et al. 2023

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“…There are PK profiles of paracetamol described for some animals such as dogs [32][33][34][35][36] and horses [37,38]. It is problematic to compare apparent clearance between species when there is no intravenous dosing PK information for the koala.…”

Section: Paracetamol Pk Profilementioning

confidence: 99%

Pharmacokinetic profile of oral and subcutaneous administration of paracetamol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy

Govendir,

Vogelnest,

Shapiro

et al. 2024

PLoS ONE

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The pharmacokinetic profile of paracetamol in koalas is described when administered orally at 15 mg/kg; followed by the same dose, administered every 12 hours (hrs), repeated five times. After the initial oral administration, the median (range) maximal plasma concentration (Cmax), the time Cmax was reached (Tmax) and elimination half-life (t1/2) were 16.93 μg/mL (13.66 to 20.25 μg/mL); 4 hrs (4 to 8 hrs) and 5.54 hrs (4.66 to 7.67 hrs), respectively. When paracetamol was administered orally at 15 mg/mL every 12 hrs, the trough total plasma concentration range remained comparable to the therapeutic range in humans i.e. 4 to 20 μg/mL that is known to provide some analgesia. However, there is a smaller proportion of free drug (i.e. not bound to plasma proteins; and the active form) available in koala plasma (approximately 40% unbound) compared to human plasma (approximately 80% unbound). Consequently, even when there are similar total drug plasma concentrations in both koala and human plasma, the therapeutic efficacy may be reduced in koalas compared to humans. The initial oral dose and subsequent twice daily doses resulted in no obvious adverse effects in any koala. Haematology, plasma electrolyte and biochemical analyte values remained within their reference ranges eight hrs after the last dose but there was a significant change in alanine transaminase (ALT) levels (an increase), and in total protein (a decrease) (both p = 0.03). A dose of 15 mg/kg was also administered as a subcutaneous injection, diluted 50:50 with saline, to two koalas. As the oral formulation and the subcutaneous administration resulted in comparable absorption, the study focused on the oral profile. Based on these results there is an argument to recommend a slight increase in the oral paracetamol dose for the koala, however further investigation is required to confirm whether repeated administration of a slightly higher dose may be associated with more severe or additional significant changes in haematology, electrolytes or biochemical analytes. However, a preferable recommendation would be to administer this dosage of paracetamol in combination with another analgesic such as tramadol, as a subcutaneous injection, to improve efficacy.

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“…La interacción de todo ser vivo está asociado con el sonido ya que es algo fundamental en la percepción espaciotemporal (Ferretti, 2006). A pesar de ello, no todo el sonido ha sido tratado de la misma manera, siempre hay circunstancias en la que ya se convierte en ruido siendo una sensación desagradable para el sentido de audición (González-Calderón et al, 2022) aún más para los animales que tienen una alta sensibilidad como los perros, así mismo, el ruido está asociado a la zona urbana, ya sea por el parque automotor, industrialización entre otros, que traen consigo consecuencias como trastornos en el sueño (Fuente-moreno et al, 2023) y aumento de cortisol debido al estrés en perros (Madsen et al, 2022).…”

Section: Introductionunclassified

Una revisión del impacto del ruido en perros entre 2018 al 2023

Rojas,

Pardo,

Ortega

et al. 2024

dekamuagropec

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Llamado el mejor amigo del hombre, pero no nos damos cuenta el daño que ocasiona lo que nosotros llamamos sonido para ellos es ruido, tienen una sensibilidad en los oídos tan extremas ya que son capaces de percibir con frecuencias más altas, es por ello por lo que el objetivo fue determinar los impactos del ruido en perros. La metodología utilizada para la sistematización de la información fue la declaración PRISMA 2020, para determinar el crecimiento anual de la producción científica se calculó con la herramienta digital Calcuvio y el análisis de datos se realizó con Microsoft Office Excel versión 2016 y VOSviewer versión 1.6.19. La distribución geográfica de las investigaciones por año se centró en el 2018 y 2022, el país pionero con mayor publicación fue Estados Unidos, la producción científica fue de 30.26% (crecimiento bajo), las palabras clave con el mayor número de coocurrencias fueron “stress” y “noise” y “dog” y los impactos más frecuentes del ruido en perros fueron en los cambios del comportamiento y el miedo-ansiedad. Se concluye que para futuras investigaciones se debe buscar medidas preventivas del ruido y evaluar el grado de afección en los perros.

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Effects of housing environment on oral absorption of acetaminophen in healthy Beagles

Cited by 5 publications

References 25 publications

Usefulness of the Beagle Model in the Evaluation of Paracetamol and Ibuprofen Exposure after Oral Administration to Pediatric Populations: An Exploratory Study

Usefulness of the Beagle Model in the Evaluation of Paracetamol and Ibuprofen Exposure after Oral Administration to Pediatric Populations: An Exploratory Study

Pharmacokinetic profile of oral and subcutaneous administration of paracetamol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy

Una revisión del impacto del ruido en perros entre 2018 al 2023

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