Pharmacokinetic Drug Interactions of an Orally Available TRH Analog (Rovatirelin) With a CYP3A4/5 and P-Glycoprotein Inhibitor (Itraconazole).
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ antagonists & inhibitors
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ antagonists & inhibitors
Administration, Oral
Adult
Area Under Curve
Asian People
Biological Transport
/ drug effects
Caco-2 Cells
Cytochrome P-450 CYP3A
/ metabolism
Cytochrome P-450 CYP3A Inhibitors
/ administration & dosage
Drug Elimination Routes
/ drug effects
Drug Interactions
Healthy Volunteers
Hormones
/ blood
Humans
Itraconazole
/ administration & dosage
Male
Neoplasm Proteins
/ antagonists & inhibitors
Oxazolidinones
/ administration & dosage
Permeability
/ drug effects
Pyrrolidines
/ administration & dosage
Thyrotropin-Releasing Hormone
/ analogs & derivatives
Young Adult
CYP3A4/5
P-glycoprotein
TRH analog
drug-drug interaction
itraconazole
multidrug resistance transporter 1
rovatirelin
Journal
Journal of clinical pharmacology
ISSN: 1552-4604
Titre abrégé: J Clin Pharmacol
Pays: England
ID NLM: 0366372
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
28
01
2020
accepted:
27
03
2020
pubmed:
28
5
2020
medline:
31
7
2021
entrez:
28
5
2020
Statut:
ppublish
Résumé
The effects of itraconazole on the pharmacokinetics of rovatirelin were investigated in an open-label, single-sequence drug-drug interaction study in 16 healthy subjects. Subjects were administered a single oral dose of rovatirelin (1.6 mg) on day 1 and day 15. From day 8 through 16, subjects received daily oral doses of itraconazole (200 mg/day). Concentrations of rovatirelin and (thiazolylalanyl)methylpyrrolidine (TAMP), the major metabolite of rovatirelin formed by cytochrome P450 (CYP) 3A4/5, were determined in plasma and urine. Pharmacokinetic parameters were used to evaluate the drug-drug interaction potential of rovatirelin as a victim. With coadministration, maximum concentration (C
Substances chimiques
(thiazoylalanyl)methylpyrrolidine
0
ABCG2 protein, human
0
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Cytochrome P-450 CYP3A Inhibitors
0
Hormones
0
Neoplasm Proteins
0
Oxazolidinones
0
Pyrrolidines
0
Itraconazole
304NUG5GF4
Thyrotropin-Releasing Hormone
5Y5F15120W
rovatirelin
9DL0X410PY
CYP3A5 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1314-1323Informations de copyright
© 2020, The American College of Clinical Pharmacology.
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