Equivalent Dynamic Human Brain NK1-Receptor Occupancy Following Single-Dose i.v. Fosaprepitant vs. Oral Aprepitant as Assessed by PET Imaging
Abstract
The type 1 neurokinin receptor (NK1R) antagonist aprepitant and its i.v. prodrug fosaprepitant have been approved for prevention of acute and delayed nausea and vomiting associated with chemotherapy. This study evaluated the magnitude and duration of brain NK1R occupancy over a period of 5 days after single-dose i.v. infusion of 150-mg fosaprepitant and single-dose oral administration of 165-mg aprepitant, using serial [(18)F]MK-0999 positron emission tomography (PET) in 16 healthy subjects. Each subject underwent three scans. Brain NK1R occupancy rates after i.v. fosaprepitant at time to peak concentration (T(max); ~30 min), 24, 48, and 120 h after the dose were 100, 100, ≥97, and 41-75%, respectively. After aprepitant, NK1R occupancy rates at these time points (T(max) ~4 h) were ≥99, ≥99, ≥97, and 37-76%, respectively. Aprepitant plasma concentration profiles were comparable for the two dosage forms. The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects.
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Although the plasma half-life of aprepitant is 9-13 hours, clinical effects may persist for 3-5 days.
“Although the plasma half‐life is 9‐13 hours, clinical effects may persist for 3‐5 days.”
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- Authors
- Van Laere, K., De Hoon, J., Bormans, G., Koole, M., Derdelinckx, I., De Lepeleire, I., Declercq, R., Sanabria Bohorquez, S. M., Hamill, T., Mozley, P. D., Tatosian, D., Xie, W., Liu, Y., Liu, F., Zappacosta, P., Mahon, C., Butterfield, K. L., Rosen, L. B., Murphy, M. G., Hargreaves, R. J., Wagner, J. A., & Shadle, C. R.
- Affiliations
- KU Leuven (BE)
- Universitair Ziekenhuis Leuven (BE)
- MSD (Belgium) (BE)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2012-06-27
- Volume
- 92
- Issue
- 2
- Pages
- 243-250
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2085381828
- Cited by
- 46
- References
- 14
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Nausea and vomiting management
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- fosaprepitant, aprepitant, neurokinin receptor antagonists, brain receptor binding, prodrugs, oral versus intravenous administration, nausea and vomiting prevention, chemotherapy-induced nausea and vomiting, positron emission tomography
- MeSH terms
- Aprepitant, Adult, Antiemetics, Antineoplastic Agents, Brain, Dose-Response Relationship, Drug, Female, Humans, Male, Morpholines, Nausea, Prodrugs, Therapeutic Equivalency, Vomiting, Receptors, Neurokinin-1, Positron-Emission Tomography, Young Adult, Neurokinin-1 Receptor Antagonists
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