ketoconazole and Abdominal Migraine studies

1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.

Research Excerpts

Excerpt	Relevance	Reference
"Dihydroergotamine (DHE), a proven migraine treatment, currently has product labeling warning against concomitant use of CYP3A4 inhibitors because of potential drug interactions."	2.77	Lack of drug interaction between the migraine drug MAP0004 (orally inhaled dihydroergotamine) and a CYP3A4 inhibitor in humans. ( Chang, J; Dodick, D; Febbraro, S; Forst, A; Kellerman, D; Kori, S; Taylor, G; Thomas, T; Wutann, L, 2012)
" Structure-3A4 MDI relationship studies culminated in the discovery of a difluoro analogue, (S)-N-[1-(4-fluoro-3-morpholin-4-ylphenyl)ethyl]-3-(4-fluoro-phenyl)acrylamide (2), as an orally bioavailable KCNQ2 opener free of CYP3A4 MDI."	1.32	Fluorine substitution can block CYP3A4 metabolism-dependent inhibition: identification of (S)-N-[1-(4-fluoro-3- morpholin-4-ylphenyl)ethyl]-3- (4-fluorophenyl)acrylamide as an orally bioavailable KCNQ2 opener devoid of CYP3A4 metabolism-dependent inhibiti ( Davis, CD; Dworetzky, S; Fitzpatrick, WC; Harden, D; He, H; Knox, RJ; Newton, AE; Philip, T; Polson, C; Sinz, MW; Sivarao, DV; Sun, LQ; Tertyshnikova, S; Weaver, D; Wu, YJ; Yeola, S; Zoeckler, M, 2003)
" The exercise aids in integrating all the knowledge across the drug development to suggest rationale dosing strategies; effectively communicating the impact of the prognostic factors to the clinicians/regulators; and protect against any intellectual losses due to development team changes."	1.31	Application of modeling and simulation to integrate clinical pharmacology knowledge across a new drug application. ( Gobburu, JV; Sekar, VJ, 2002)

Research

Studies (3)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

AUC(0-48) of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (66.67)	29.6817
2010's	1 (33.33)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Wu, YJ	1
Davis, CD	1
Dworetzky, S	1
Fitzpatrick, WC	1
Harden, D	1
He, H	1
Knox, RJ	1
Newton, AE	1
Philip, T	1
Polson, C	1
Sivarao, DV	1
Sun, LQ	1
Tertyshnikova, S	1
Weaver, D	1
Yeola, S	1
Zoeckler, M	1
Sinz, MW	1
Kellerman, D	1
Kori, S	1
Forst, A	1
Chang, J	1
Febbraro, S	1
Wutann, L	1
Thomas, T	1
Taylor, G	1
Dodick, D	1
Gobburu, JV	1
Sekar, VJ	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase I Evaluation of the Effect of Ketoconazole on the Pharmacokinetics and Safety of Dihydroergotamine Mesylate (DHE) Delivered by Oral Inhalation (MAP0004) in Healthy Volunteers Compared to DHE Delivered Intravenously (DHE 45®)[NCT01468558]	Phase 1	24 participants (Actual)	Interventional	2010-07-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The AUC(0-48) is the area under the plot of plasma concentration of drug against time after drug administration. Dihydroergotamine AUC(0-48) is reported in picograms times hour per milliliter (pg*h/ml). (NCT01468558)
Timeframe: 48 hours

Cmax of Dihydroergotamine After MAP0004, MAP0004 Co-administered With Ketoconazole, and IV DHE Administration

Intervention	pg*h/ml (Geometric Mean)
MAP0004 1.0mg	3484.725
MAP0004 1.0mg + Ketoconazole	4070.611
IV DHE 1.0mg	9229.171

The maximum concentration (Cmax) is the highest concentration of a drug measured in the plasma. Plasma is the clear portion of the blood. The Cmax of Dihydroergotamine is reported in picograms per milliliter (pg/ml). (NCT01468558)
Timeframe: 48 hours

Intervention	pg/ml (Geometric Mean)
MAP0004 1.0mg	2582.507
MAP0004 1.0mg + Ketoconazole	2495.100
IV DHE 1.0mg	27771.234

ketoconazole and Abdominal Migraine