ArticlePharmaceutical research2014
Pharmacokinetics of paracetamol in Göttingen minipigs: in vivo studies and modeling to elucidate physiological determinants of absorption.
Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 35 citations in OpenAlex.
- Safety, tolerability and toxicokinetics of the novel mitochondrial drug SUL-138 administered orally to rat and minipig.Toxicology reports · 2024Article
- SmartPill™ Administration to Assess Gastrointestinal Function after Spinal Cord Injury in a Porcine Model-A Preliminary Study.Biomedicines · 2023Article
- Population pharmacokinetic of paracetamol and atorvastatin with co-administration of semaglutide.Pharmacology research & perspectives · 2022Article
- The Effect of Amino Acids on Production of SCFA and bCFA by Members of the Porcine Colonic Microbiota.Microorganisms · 2022Article
- Article
- Hepatic Cytochrome P450 Abundance and Activity in the Developing and Adult Göttingen Minipig: Pivotal Data for PBPK Modeling.Frontiers in pharmacology · 2021Article
- The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development.Pharmaceutics · 2020Review
- Toward the establishment of a standardized pre-clinical porcine model to predict food effects - Case studies on fenofibrate and paracetamol.International journal of pharmaceutics: X · 2019Article
- Postprandial Amino Acid Kinetics of Milk Protein Mixtures are Affected by Composition, But Not Denaturation, in Neonatal Piglets.Current developments in nutrition · 2019Article
- Characterization of Pharmacokinetics in the Göttingen Minipig with Reference Human Drugs: An In Vitro and In Vivo Approach.Pharmaceutical research · 2016Article
- Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle.The Journal of veterinary medical science · 2016Article
- In silico screening for novel inhibitors of DNA polymerase III alpha subunit of Mycobacterium tuberculosis (MtbDnaE2, H37Rv).PloS one · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOnset and rate of gastric emptying are important determinants of drug absorption after oral dosing. Therefore, robust estimates of these parameters are needed in physiologically based absorption models to predict reliably plasma concentration time profiles. For human and some other laboratory animals, reasonable parameterization of gastric emptying has been established. However gastric emptying is less well characterized in minipigs, a large animal model rapidly gaining importance in pharmaceutical research.
methodsA pharmacokinetic crossover study using different dosage forms of paracetamol (intravenous and oral solution, capsule and tablet) was conducted in four male and four female Göttingen minipigs after an overnight fast. Deconvolution analysis was performed to determine the absorption kinetics. Estimated lag times and first order gastric emptying parameters were incorporated in a previously published PBPK model of the minipig and simulations verified. Postmortem assessments of minipig stomachs were made after different fasting protocols.
resultsFraction of dose absorbed vs. time profiles showed high interindividual variability, comparable to human fed state absorption. Mean gastric transit times were determined to be 0.63 h, 1.36 h, and 0.73 h for solution, capsules, and tablets, respectively. Postmortem assessment confirmed that minipig stomachs were not empty after an overnight fast.
conclusionsGastric transit times in overnight fasted minipigs are longer than those observed in humans. This is most likely caused by delayed and incomplete food emptying and further work is needed to develop feasible and effective fasting protocols for minipigs.
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