| Title |
Assessment of Juvenile Pigs to Serve as Human Pediatric Surrogates for Preclinical Formulation Pharmacokinetic Testing
|
|---|---|
| Published in |
The AAPS Journal, April 2013
|
| DOI | 10.1208/s12248-013-9482-6 |
| Pubmed ID | |
| Authors |
Wyatt J. Roth, Candice B. Kissinger, Robyn R. McCain, Bruce R. Cooper, Jeremy N. Marchant-Forde, Rachel C. Vreeman, Sophia Hannou, Gregory T. Knipp |
| Abstract |
Pediatric drug development is hampered by biological, clinical, and formulation challenges associated with age-based populations. A primary cause for this lack of development is the inability to accurately predict ontogenic changes that affect pharmacokinetics (PK) in children using traditional preclinical animal models. In response to this issue, our laboratory has conducted a proof-of-concept study to investigate the potential utility of juvenile pigs to serve as surrogates for children during preclinical PK testing of selected rifampin dosage forms. Pigs were surgically modified with jugular vein catheters that were externalized in the dorsal scapular region and connected to an automated blood sampling system (PigTurn-Culex-L). Commercially available rifampin capsules were administered to both 20 and 40 kg pigs to determine relevant PK parameters. Orally disintegrating tablet formulations of rifampin were also developed and administered to 20 kg pigs. Plasma samples were prepared from whole blood by centrifugation and analyzed for rifampin content by liquid chromatography-tandem mass spectrometry. Porcine PK parameters were determined from the resultant plasma-concentration time profiles and contrasted with published rifampin PK data in human adults and children. Results indicated significant similarities in dose-normalized absorption and elimination parameters between pigs and humans. Moreover, ontogenic changes observed in porcine PK parameters were consistent with ontogenic changes reported for human PK. These results demonstrate the potential utility of the juvenile porcine model for predicting human pediatric PK for rifampin. Furthermore, utilization of juvenile pigs during formulation testing may provide an alternative approach to expedite reformulation efforts during pediatric drug development. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 2% |
| Unknown | 43 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 23% |
| Student > Ph. D. Student | 9 | 20% |
| Student > Bachelor | 3 | 7% |
| Student > Postgraduate | 3 | 7% |
| Student > Master | 3 | 7% |
| Other | 7 | 16% |
| Unknown | 9 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 12 | 27% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 11% |
| Biochemistry, Genetics and Molecular Biology | 4 | 9% |
| Agricultural and Biological Sciences | 3 | 7% |
| Chemistry | 2 | 5% |
| Other | 6 | 14% |
| Unknown | 12 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 February 2023.
All research outputs
#6,461,883
of 23,342,092 outputs
Outputs from The AAPS Journal
#353
of 1,304 outputs
Outputs of similar age
#53,625
of 199,022 outputs
Outputs of similar age from The AAPS Journal
#8
of 13 outputs
Altmetric has tracked 23,342,092 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,304 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 199,022 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.