Veterinary Pharmacology

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Jonathan P. Mochel - One of the best experts on this subject based on the ideXlab platform.

  • Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed-Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats.
    CPT: pharmacometrics & systems pharmacology, 2016
    Co-Authors: Ludovic Pelligand, Antoine Soubret, Jonathan N. King, Jonathan Elliott, Jonathan P. Mochel
    Abstract:

    The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first-order absorption best described robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip-flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population.

  • mathematical modeling and simulation in animal health part ii principles methods applications and value of physiologically based pharmacokinetic modeling in Veterinary medicine and food safety assessment
    Journal of Veterinary Pharmacology and Therapeutics, 2016
    Co-Authors: Zhoumeng Lin, Jonathan P. Mochel, Ronette Gehring, T Lave, Jim E Riviere
    Abstract:

    This review provides a tutorial for individuals interested in quantitative Veterinary Pharmacology and toxicology and offers a basis for establishing guidelines for physiologically based pharmacokinetic (PBPK) model development and application in Veterinary medicine. This is important as the application of PBPK modeling in Veterinary medicine has evolved over the past two decades. PBPK models can be used to predict drug tissue residues and withdrawal times in food-producing animals, to estimate chemical concentrations at the site of action and target organ toxicity to aid risk assessment of environmental contaminants and/or drugs in both domestic animals and wildlife, as well as to help design therapeutic regimens for Veterinary drugs. This review provides a comprehensive summary of PBPK modeling principles, model development methodology, and the current applications in Veterinary medicine, with a focus on predictions of drug tissue residues and withdrawal times in food-producing animals. The advantages and disadvantages of PBPK modeling compared to other pharmacokinetic modeling approaches (i.e., classical compartmental/noncompartmental modeling, nonlinear mixed-effects modeling, and interspecies allometric scaling) are further presented. The review finally discusses contemporary challenges and our perspectives on model documentation, evaluation criteria, quality improvement, and offers solutions to increase model acceptance and applications in Veterinary Pharmacology and toxicology.

  • Multiple comparison procedure and modeling: a versatile tool for evaluating dose-response relationships in Veterinary Pharmacology - a case study with furosemide.
    Journal of Veterinary Pharmacology and Therapeutics, 2016
    Co-Authors: Bruno Bieth, B. Bornkamp, Céline E. Toutain, R. Garcia, Jonathan P. Mochel
    Abstract:

    : Congestive heart failure (CHF) is a leading cause of mortality with an increasing prevalence in human and canine populations. While furosemide is a loop diuretic prescribed for the majority of CHF patients to reduce fluid retention, it also activates the renin-angiotensin aldosterone system (RAAS) which further contributes to the accelerated progression of heart failure. Our objective was to quantify the effect of furosemide on diuresis, renin activity (RA), and aldosterone (AL) in dogs, using a combined multiple comparisons and model-based approach (MCP-Mod). Twenty-four healthy beagle dogs were allocated to four treatment groups (saline vs. furosemide 1, 2, and 4 mg/kg i.m., q12 h for 5 days). Data from RA and AL values at furosemide trough concentrations, as well as 24-h Diuresis, were analyzed using the MCP-Mod procedure. A combination of Emax models adequately described the dose-response relationships of furosemide for the various endpoints. The dose-response curves of RA and AL were found to be well in agreement, with an apparent shallower slope compared with 24-h Diuresis. The research presented herein constitutes the first application of MCP-Mod in Veterinary Medicine. Our data show that furosemide produces a submaximal effect on diuresis at doses lower than those identified to activate the circulating RAAS.

  • position paper eufeps network on Veterinary medicines initiative an interdisciplinary forum to support Veterinary Pharmacology and promote the development of new pharmaceuticals for animal health
    European Journal of Pharmaceutical Sciences, 2016
    Co-Authors: Lennart Dencker, Jonathan P. Mochel, K Hellmann, S Senel, Eva Tyden, Johannes Cornelis Vendrig, Hans H Linden, I Schmerold
    Abstract:

    Veterinary medicines account for a substantial portion of the production, sale, and consumption of medicines in Europe, and probably world-wide. This calls our attention to the fact that only healt ...

  • animal health modeling simulation society a new society promoting model based approaches in Veterinary Pharmacology
    Journal of Veterinary Pharmacology and Therapeutics, 2013
    Co-Authors: Jonathan P. Mochel, Ludovic Pelligand, Ronette Gehring, Johan Gabrielsson, Wendy Collard, Martin Fink, Celine M Laffont, Yahong Liu, Tomas Martinjimenez, Jeanlouis Steimer
    Abstract:

    The Animal Health Modeling & Simulation Society (AHM&S) is a newly founded association (2012) that aims to promote the development, application, and dissemination of modeling and simulation techniques in the field of Veterinary Pharmacology and Toxicology. The association is co-chaired by Pr. Johan Gabrielsson (Europe), Pr. Jim Riviere (USA), and secretary Dr. Jonathan Mochel (Switzerland). This short communication aims at presenting the membership, rationale and objectives of this group.

Jim E Riviere - One of the best experts on this subject based on the ideXlab platform.

Walkenhorst Michael - One of the best experts on this subject based on the ideXlab platform.

  • EthnoVeterinary contemporary knowledge of farmers in pre-alpine and alpine regions of the Swiss cantons of Bern and Lucerne compared to ancient and recent literature – Is there a tradition?
    'Elsevier BV', 2019
    Co-Authors: Stucki Karin, Dal Cero Maja, Vogl, Christian R., Ivemeyer Silvia, Meier Beat, Maeschli Ariane, Hamburger Matthias, Walkenhorst Michael
    Abstract:

    Ethnopharmacological relevance The term “traditional” is well established in European (human) medicine and even appears in recent European regulations on herbal medicinal products connected to a simplified registration. In contrast, a scientific discussion of a Traditional European Veterinary Herbal Medicine is still lacking in spite of a rising interest, in herbal medicine for animals in particular of veterinarians. There is only limited systematic ethnoVeterinary research in Europe, with exception of the Mediterranean region, Switzerland and Austria. We conducted a survey on the ethnoVeterinary knowledge of farmers in the pre-alpine and alpine regions of the Swiss cantons of Bern and Lucerne. We compared the findings with earlier studies conducted in Switzerland and with recent and past human and Veterinary medicinal literature. Aim of the study We wanted to know to what extent (dependent to different definition of the term “traditional”) the ethnoVeterinary knowledge of Swiss farmers could be considered as “traditional” in a European Veterinary medicinal context. Material and methods Semistructured interviews with 44 dialog partners, mainly smallholder cattle farmers, were conducted in 2014. Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers satisfaction) were collected. To compare our data with literature, one German book of Veterinary Pharmacology published in 1900, one typescript of Swiss lectures in Veterinary Pharmacology from 1944, four books of Veterinary herbal medicine published between 1984 and 2016, and one recent publication comparing current Swiss (human) ethnomedicinal plant knowledge with modern and past literature were analyzed. Results Information on a total of 315 homemade remedies containing one single plant species (homemade single species herbal remedy reports, HSHR) was collected from participating farmers. These HSHR were prepared from 83 plant species belonging to 46 botanical families. Plants of the families Asteraceae, Lamiaceae and Rosaceae were most frequently used. Matricaria recutita L., Calendula officinalis L., Quercus robur L., Thymus vulgaris L. and Symphytum officinale L. were the most frequently documented species. A total of 404 use reports (UR) were gathered for the 315 HSHR. The largest number of UR was for treatments of gastrointestinal disorders and metabolic dysfunctions, followed by skin alterations and sores. For more than half of the UR the source of knowledge was family, ancestors and friends, and for approximately one quarter the information was from courses and other educational events. For nearly 90% of the UR farmers mentioned at least one use during the last 10 years, and in more than 50% of the UR the last use was within the past year. Compared with recent and past literature and depending on different definitions of the term “traditional” as used for human medicine between 43% and 84% of all 83 and between 57% and 100% of the most often mentioned 21 plant species show a “traditional” European Veterinary use. Conclusion For the treatment of their animals farmers in the pre-alpine and alpine regions of the Swiss cantons of Bern and Lucerne mostly used plants which have a track record as medicinal herbs in Europe over several centuries. Almost half of the plant species had specific Veterinary uses for about 120 years and even more for at least 30 years. The majority of the plant species thus fulfill the criteria of “traditional” according to several definitions and even more up to a certain degree the criteria of “traditional use” as defined in European regulations for human medicinal products. EthnoVeterinary research combined with data from historical sources may serve as a sound foundation for the development and definition of a Traditional European Veterinary Herbal Medicine maybe even with regard to the recent discussion about a simplified registration for Traditional Herbal Veterinary Medicinal Products

  • EthnoVeterinary knowledge of farmers in pre-alpine and alpine regions of the Swiss cantons of Bern and Lucerne compared to ancient and recent literature - is there a tradition?
    'Elsevier BV', 2019
    Co-Authors: Stucki Karin, Dal Cero Maja, Vogl, Christian R., Ivemeyer Silvia, Meier Beat, Maeschli Ariane, Hamburger Matthias, Walkenhorst Michael
    Abstract:

    Ethnopharmacological relevance: The term “traditional” is well established in European (human) medicine and even appears in recent European regulations on herbal medicinal products connected to a simplified registration. In contrast, a scientific discussion of a Traditional European Veterinary Herbal Medicine is still lacking in spite of a rising interest, in herbal medicine for animals in particular of veterinarians. There is only limited systematic ethnoVeterinary research in Europe, with exception of the Mediterranean region, Switzerland and Austria. We conducted a survey on the ethnoVeterinary knowledge of farmers in the pre-alpine and alpine regions of the Swiss cantons of Bern and Lucerne. We compared the findings with earlier studies conducted in Switzerland and with recent and past human and Veterinary medicinal literature. Aim of the study: We wanted to know to what extent (dependent to different definition of the term “traditional”) the ethnoVeterinary knowledge of Swiss farmers could be considered as “traditional” in a European Veterinary medicinal context. Material and methods: Semistructured interviews with 44 dialog partners, mainly smallholder cattle farmers, were conducted in 2014. Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers satisfaction) were collected. To compare our data with literature, one German book of Veterinary Pharmacology published in 1900, one typescript of Swiss lectures in Veterinary Pharmacology from 1944, four books of Veterinary herbal medicine published between 1984 and 2016, and one recent publication comparing current Swiss (human) ethnomedicinal plant knowledge with modern and past literature were analyzed. Results: Information on a total of 315 homemade remedies containing one single plant species (homemade single species herbal remedy reports, HSHR) was collected from participating farmers. These HSHR were prepared from 83 plant species belonging to 46 botanical families. Plants of the families Asteraceae, Lamiaceae and Rosaceae were most frequently used. Matricaria recutita L., Calendula officinalis L., Quercus robur L., Thymus vulgaris L. and Symphytum officinale L. were the most frequently documented species. A total of 404 use reports (UR) were gathered for the 315 HSHR. The largest number of UR was for treatments of gastrointestinal disorders and metabolic dysfunctions, followed by skin alterations and sores. For more than half of the UR the source of knowledge was family, ancestors and friends, and for approximately one quarter the information was from courses and other educational events. For nearly 90% of the UR farmers mentioned at least one use during the last 10 years, and in more than 50% of the UR the last use was within the past year. Compared with recent and past literature and depending on different definitions of the term “traditional” as used for human medicine, between 43% and 84% of all 83 and between 57% and 100% of the most often mentioned 21 plant species show a “traditional” European Veterinary use. Conclusion: For the treatment of their animals farmers in the pre-alpine and alpine regions of the Swiss cantons of Bern and Lucerne mostly used plants which have a track record as medicinal herbs in Europe over several centuries. Almost half of the plant species had specific Veterinary uses for about 120 years and even more for at least 30 years. The majority of the plant species thus fulfill the criteria of “traditional” according to several definitions and even more up to a certain degree the criteria of “traditional use” as defined in European regulations for human medicinal products. EthnoVeterinary research combined with data from historical sources may serve as a sound foundation for the development and definition of a Traditional European Veterinary Herbal Medicine maybe even with regard to the recent discussion about a simplified registration for Traditional Herbal Veterinary Medicinal Products

Ludovic Pelligand - One of the best experts on this subject based on the ideXlab platform.

  • Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed-Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats.
    CPT: pharmacometrics & systems pharmacology, 2016
    Co-Authors: Ludovic Pelligand, Antoine Soubret, Jonathan N. King, Jonathan Elliott, Jonathan P. Mochel
    Abstract:

    The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects. A bicompartmental disposition model with simultaneous zero and first-order absorption best described robenacoxib PKs in blood. Clearance was 0.502 L/kg/h and the bioavailability was high (78%). The absorption constant point estimate (Ka = 0.68 h−1) was lower than beta (median, 1.08 h−1), unveiling flip-flop kinetics. No dosing adjustment based on available covariates information is advocated. This modeling work constitutes the first application of NLME in a large feline population.

  • animal health modeling simulation society a new society promoting model based approaches in Veterinary Pharmacology
    Journal of Veterinary Pharmacology and Therapeutics, 2013
    Co-Authors: Jonathan P. Mochel, Ludovic Pelligand, Ronette Gehring, Johan Gabrielsson, Wendy Collard, Martin Fink, Celine M Laffont, Yahong Liu, Tomas Martinjimenez, Jeanlouis Steimer
    Abstract:

    The Animal Health Modeling & Simulation Society (AHM&S) is a newly founded association (2012) that aims to promote the development, application, and dissemination of modeling and simulation techniques in the field of Veterinary Pharmacology and Toxicology. The association is co-chaired by Pr. Johan Gabrielsson (Europe), Pr. Jim Riviere (USA), and secretary Dr. Jonathan Mochel (Switzerland). This short communication aims at presenting the membership, rationale and objectives of this group.

Pierre-louis Toutain - One of the best experts on this subject based on the ideXlab platform.

  • Veterinary Pharmacology: history, current status and future prospects.
    Journal of Veterinary Pharmacology and Therapeutics, 2013
    Co-Authors: P Lees, Johanna Fink-gremmels, Pierre-louis Toutain
    Abstract:

    Veterinary therapeutics, based on the art of Materia Medica, has been practised for countless centuries, but the science of Veterinary Pharmacology is of very recent origin. This review traces the contribution of Materia Medica to Veterinary therapeutics from the Egyptian period through to the Age of Enlightenment. The first tentative steps in the development of the science of Veterinary Pharmacology were taken in the 18th century, but it was not until the mid 20th century that the science replaced the art of Materia Medica. This review traces the 20th century developments in Veterinary Pharmacology, with emphasis on the explosion of knowledge in the 35 year period to 2010. The range of factors which have influenced the current status of the discipline are reviewed. Future developments are considered from the perspectives of what might be regarded as desirable and those innovations that might be anticipated. We end with words of encouragement for young colleagues intent upon pursuing a career in Veterinary Pharmacology.

  • PK-PD integration and PK-PD modelling of nonsteroidal anti-inflammatory drugs: Principles and applications in Veterinary Pharmacology
    Journal of Veterinary Pharmacology and Therapeutics, 2004
    Co-Authors: Peter Lees, J. Giraudel, M F Landoni, Pierre-louis Toutain
    Abstract:

    Much useful information relevant to elucidation of mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) at the molecular level can be obtained from integrating pharmacokinetic (PK) and pharmacodynamic (PD) data, such data being obtained usually, although not necessarily, in separate studies. Integrating PK and PD data can also provide a basis for selecting clinically relevant dosing schedules for subsequent evaluation in disease models and clinical trials. The principles underlying and uses of PK-PD integration are illustrated in this review for phenylbutazone in the horse and cow, carprofen and meloxicam in the horse, carprofen and meloxicam in the cat and nimesulide in the dog. In the PK-PD modelling approach for NSAIDs, the PK and PD data are generated (usually though not necessarily) in vivo in the same investigation and then modelled in silico, usually using the integrated effect compartment or indirect response models. Drug effect is classically modelled with the sigmoidal E(max) (Hill) equation to derive PD parameters which define efficacy, potency and sensitivity. The PK-PD modelling approach for NSAIDs can be undertaken at the molecular level using surrogates of inhibition of cyclooxygenase (COX) isoforms (or indeed other enzymes e.g. 5-lipoxygenase). Examples are provided of the generation of PD parameters for several NSAIDs (carprofen, ketoprofen, vedaprofen, flunixin and tolfenamic acid) in species of Veterinary interest (horse, calf, sheep and goat), which indicate that all drugs investigated except vedaprofen were non-selective for COX-1 and COX-2 in the four species investigated under the experimental conditions used, vedaprofen being a COX-1 selective NSAID. In these studies, plasma concentration was linked to COX inhibitory action in the biophase using an effect compartment model. Data for S-(+)-ketoprofen have been additionally subjected to inter-species modelling and allometric scaling of both PK and PD parameters. For several species values of four PK parameters were highly correlated with body weight, whilst values for PD parameters based on COX inhibition lacked allometric relationship with body weight. PK-PD modelling of NSAIDs has also been undertaken using clinical end-points and surrogates for clinical end-points in disease models. By measurement of clinically relevant indices in clinically relevant models, data generated for PD parameters have been used to set dosages and dose intervals for evaluation and confirmation in clinical trials. PK-PD modelling of NSAIDs is likely to prove superior to conventional dose titration studies for dosage schedule determination, as it sweeps the whole of the concentration-effect relationship for all animals and therefore permits determination of genuine PD parameters. It also introduces time as a second independent variable thus allowing prediction of dosage interval. Using indirect response models and clinically relevant indices, PD data have been determined for flunixin, phenylbutazone and meloxicam in the horse, nimesulide in the dog and meloxicam in the cat.