Exploring gastric emptying rate in minipigs: Effect of food type and pre-dosing of metoclopramide

Henze, Laura J.; Griffin, Brendan T.; Christiansen, M. Skytte; Bundgaard, Christoffer; Langguth, Peter; Holm, René

doi:10.1016/j.ejps.2018.03.017

Cited by 15 publications

(15 citation statements)

References 27 publications

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“…In metoclopramide pre‐treated pigs, the weight of the stomach contents was lower compared to the non‐treated groups, suggesting that this is a potential approach to mimic a fasted state condition. In contrast, however, a recent study by Henze et al . did not observe an effect of pre‐treating with metoclopramide on the gastric emptying rate in minipigs, based upon analysis of paracetamol absorption both in the fasted and different fed state conditions (FDA breakfast vs nutritional drink vs normal pig food).…”

Section: Comparing the Gastrointestinal Tract Of Pigs And Humansmentioning

confidence: 80%

The pig as a preclinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms: a PEARRL review

Henze

Koehl

O’Shea

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives In pharmaceutical drug development, preclinical tests in animal models are essential to demonstrate whether the new drug is orally bioavailable and to gain a first insight into in vivo pharmacokinetic parameters that can subsequently be used to predict human values. Despite significant advances in the development of bio-predictive in vitro models and increasing ethical expectations for reducing the number of animals used for research purposes, there is still a need for appropriately selected pre-clinical in vivo testing to provide guidance on the decision to progress to testing in humans. The selection of the appropriate animal models is essential both to maximise the learning that can be obtained from such experiments and to avoid unnecessary testing in a range of species. Key findings The present review, provides an insight into the suitability of the pig model for predicting oral bioavailability in humans, by comparing the conditions in the GIT. It also contains a comparison between the bioavailability of compounds dosed to both humans and pigs, to provide an insight into the relative correlation and examples on why a lack of correlation may be observed. Summary While there is a general trend towards predicting human bioavailability from pig data, there is considerable variability in the data set, most likely reflecting species specific differences in individual drug metabolism. Nonetheless, the correlation between pigs vs. humans was comparable to that reported for dogs vs. humans. The presented data demonstrate the suitability of the pig as a preclinical model to predict bioavailability in human.

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Section: Comparing the Gastrointestinal Tract Of Pigs And Humansmentioning

confidence: 80%

The pig as a preclinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms: a PEARRL review

Henze

Koehl

O’Shea

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Dogs are indeed the most widely characterised animal model in food effect studies, and dog specific food effect models are widely available, with a general tendency to be overpredictive of human food effect . In contrast, a recent study exploring food effect in mini‐pigs suggest the Göttingen mini‐pig model is less suited for exploring food effect interactions studies than other species …”

Section: Strategies To Overcome Food Effect Bioavailability In Drug Dmentioning

confidence: 99%

Food for thought: formulating away the food effect – a PEARRL review

O’Shea

Holm

O’Driscoll

et al. 2018

Journal of Pharmacy and Pharmacology

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There are clinical and commercial advantages to predicting the presence of food effects early in the drug development process, in order to mitigate this risk of variable food effect bioavailability. Formulation approaches aimed at reducing variable food-dependent bioavailability, through the use of bio-enabling formulations, are an essential tool in addressing this challenge and the latest state of the art in this field are summarised here.

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“…What is wanting in this study, clearly, as should be made obvious from this review in general, is standardization of procedures and, to the extent possible, choice of pig breed. More recent attempts to investigate this issue using, for example, acetaminophen as a marker compound for GE have rather convincingly demonstrated, under the reported experimental conditions, that pigs have a prolonged GE, food remains in the stomach (even after fasting for many hours; confirmed by postmortem inspection), and protocols to resolve this concern (e.g., administration of GIT stimulants, such as metoclopramide) may not be appropriate or always work (Suenderhauf et al, 2014;Christiansen et al, 2015;Henze et al, 2018). Lack of a food effect, when expected or noted in humans for specific drugs and not found in pigs, using the Food and Drug Administration-approved high-fat content meal (often used in the dog), would suggest that the pig is not, under current protocols, a reliable animal model.…”

Section: Gastric Emptying and Intestinal Transitmentioning

confidence: 99%

“…Disadvantages also exist for the dog in this regard, which is the most often relied upon model. We have also cited several publications that have examined the drug absorption process in the minipig (e.g., Suenderhauf et al, 2014;Henze et al, 2018). In this section, we discuss several other specific examples in which drug dosage forms have been assessed in the pig and for which there are relevant human data.…”

Section: Evaluation Of Formulationsmentioning

confidence: 99%

Porcine Prediction of Pharmacokinetic Parameters in People: A Pig in a Poke?

Tang

Mayersohn

2018

Drug Metab Dispos

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The minipig has become an animal of considerable interest in preclinical drug development. It has been used in toxicology research and in examining/establishing regulatory guidelines as a nonrodent animal model. We have reviewed some basic issues that one would want to consider in the development and testing of any animal model for humans. The pig is a reasonable alternative to the dog, but there are some clear limitations and unexplained disparities in the literature, which require further study; primary among these is the need for standardization in choice of breed and sex and routine protocols. The minipig offers numerous advantages over other established animal models, and it has similarities to the human with regard to anatomy, physiology, and biochemistry. The gastrointestinal tract is structurally and functionally similar to humans. This appears to be true for enzymes and transporters in the gut as well, but more study is needed. One major concern is assessment of oral drug absorption, especially with regard to potential food effects due to gastric emptying differences, yet this does not appear to be a consistent observation. Hepatic metabolism seems to reflect enzymatic patterns in humans, with some differences. Kidney function seems similar to humans but requires further study. We have analyzed literature data that suggest the pig would offer a reasonable model for human oral bioavailability and for allometric predictions of clearance. The minipig appears to be the model for dermal absorption in humans, and we discuss this in terms of literature data and our own in-house experience.

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Exploring gastric emptying rate in minipigs: Effect of food type and pre-dosing of metoclopramide

Cited by 15 publications

References 27 publications

The pig as a preclinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms: a PEARRL review

The pig as a preclinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms: a PEARRL review

Food for thought: formulating away the food effect – a PEARRL review

Porcine Prediction of Pharmacokinetic Parameters in People: A Pig in a Poke?

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