Comparative Pharmacokinetics Studies of Immediate- and Modified-Release Formulations of Glipizide in Pigs and Dogs

Kulkarni, Rajesh; Yumibe, Nathan; Wang, Zhongyi; Zhang, Xin; Tang, Chengxuan; Ruterbories, Kenneth J.; Cox, Amy L.; McCain, Robyn; Knipp, Gregory T.

doi:10.1002/jps.23292

Cited by 9 publications

(3 citation statements)

References 38 publications

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“…For formulations with glipizide, the pig was reported to be a suitable model to predict modified release formulation performance. Kulkarni et al . reported that the porcine absorption kinetics were consistent with the published clinical data, conversely the beagle dog was less consistent compared to humans.…”

Section: The Use Of the Pig Model For Assessing In Vivo Performance Omentioning

confidence: 73%

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. 2019

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: The Use Of the Pig Model For Assessing In Vivo Performance Omentioning

confidence: 73%

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. 2019

Journal of Pharmacy and Pharmacology

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show abstract

“…Domesticated swine weighing up to 50 kg have been used in research studies in our laboratories, and miniature pigs have also been utilized in preclinical testing because they are easy to handle (41). In a comparative PK study of glipizide, pig and dog models were used for immediate and modified release formulations (42). For the 10 mg modified release formulation, pigs showed a more consistent exposure with a coefficient of variance of 54% which was lower compared to dogs (80%).…”

Section: Inadequacy Of Preclinical Modelsmentioning

confidence: 99%

Pediatric Formulations: Knowledge Gaps Limiting the Expedited Preclinical to Clinical Translation in Children

2019

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Traditionally, drug discovery and development research have been primarily focused on the mitigation of disease treatment for the general adult population, often overlooking the medical needs of pediatric patients. While remarkable progress toward the discovery of better medicines has been made, the pharmacological differences between children and adults are often neglected as part of the translation process. In fact, until recently, children have been considered therapeutic orphans due to the lack of significant drug discovery, formulation development, and dosage form design specifically tailored for pediatric patients. Perhaps the least understood is the significant physiological changes that occur during the maturation process from birth to adulthood. It requires careful considerations to achieve age-specific-desired therapeutic outcomes with minimal toxicity. This introduces considerable risk into the preclinical and clinical testing of new medicaments, which until recently, was avoided based on the conventional approach where a demonstration of safe and efficacious use in adults over several years potentially would minimize the chance of adverse juvenile responses. However, the lack of appropriate drug products for children has led to off-label use of adult medicines with potential life-threatening adverse reactions and health complications. Recent developments and future considerations regarding pediatric drug discovery and development using a patient-centric approach in the context of ontogenic biopharmaceutical considerations are discussed below.

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“…Drug absorption from modified (i.e., controlled or sustained) release dosage forms has been examined in numerous studies. Kulkarni et al (2012) compared the absorption of immediate and modified release in immature farm pigs (;3.5-4 months; 21-27 kg) and dogs (apparently under fasting conditions). The results suggested that the pig may be more suitable an animal model on the basis of smaller variance in area under the plasma concentration-time curve (AUC) and a higher BA (;80%, similar to humans).…”

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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Comparative Pharmacokinetics Studies of Immediate- and Modified-Release Formulations of Glipizide in Pigs and Dogs

Cited by 9 publications

References 38 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

Pediatric Formulations: Knowledge Gaps Limiting the Expedited Preclinical to Clinical Translation in Children

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

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