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Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives
- Source :
- Experimental Biology and Medicine. 242:1178-1184
- Publication Year :
- 2017
- Publisher :
- SAGE Publications, 2017.
-
Abstract
- Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved Impact statement One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding pharmacologic characteristics of the drug in drug development.
- Subjects :
- 0301 basic medicine
Fenretinide
Antineoplastic drug
Administration, Oral
Antineoplastic Agents
macromolecular substances
Pharmacology and Toxicology
Pharmacology
Lymphoma, T-Cell
Synthetic retinoid
General Biochemistry, Genetics and Molecular Biology
Neuroblastoma
03 medical and health sciences
chemistry.chemical_compound
Clinical Trials, Phase II as Topic
0302 clinical medicine
Pharmacokinetics
Humans
Medicine
Cytotoxic T cell
Infusions, Intravenous
Cytotoxicity
Clinical Trials, Phase I as Topic
business.industry
carbohydrates (lipids)
Clinical trial
Treatment Outcome
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Cancer cell
bacteria
business
Subjects
Details
- ISSN :
- 15353699 and 15353702
- Volume :
- 242
- Database :
- OpenAIRE
- Journal :
- Experimental Biology and Medicine
- Accession number :
- edsair.doi.dedup.....b17ba0598d26223fc5c44b6770f64324