A highly sensitive and selective high-performance liquid chromatographic method, involving sample pre-treatment, column switching and fluorimetric detection, is described for the determination of dihydroergotamine in plasma and urine samples. The pre-chromatographic sample treatment consists of extraction by means of an Extrelut column for plasma samples, and pre-separation with enrichment steps on a Sep-Pak column for urine samples. The samples are then injected onto a pre-separation column (Aquapore), and the fraction containing dihydroergotamine are automatically diverted onto an analytical column (ODS reversed phase). An acetonitrile-ammonium carbamate gradient is used as the mobile phase. High recovery of dihydroergotamine from both plasma (87%) and urine (100%) and a detection limit as low as 100 pg/ml were achieved, with a linear response up to 5 ng/ml. The assay demonstrated a high degree of selectivity with regard to the extensive metabolism of dihydroergotamine especially to the main metabolite 8'-hydroxydihydroergotamine. The assay was successfully applied for more than one year to the determination of plasma and urine concentrations of dihydroergotamine after parenteral administration.
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http://dx.doi.org/10.1016/0378-4347(87)80125-1 | DOI Listing |
Headache
November 2024
Satsuma Pharmaceuticals, Inc., Durham, North Carolina, USA.
Objective: To assess the relationships between dihydroergotamine (DHE) pharmacokinetic (PK) parameters, clinical efficacy, and nausea incidence to determine a DHE PK profile that optimizes efficacy while minimizing adverse events (AEs), particularly nausea.
Background: Dihydroergotamine is a widely used option for the acute treatment of migraine. Although multiple DHE dosage forms, with varying PK and AE profiles, have been evaluated in randomized controlled trials (RCTs), the relationships between PK profile, efficacy, and the common DHE-related AE, nausea, have not been comprehensively evaluated.
CNS Neurol Disord Drug Targets
September 2024
Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110 062, India.
Headache
June 2024
Pulmatrix Inc., Bedford, Massachusetts, USA.
Background: Intravenous dihydroergotamine (DHE) has well-established efficacy for the acute treatment of migraine, but its use is limited by the need for in-hospital administration and the nausea/vomiting associated with a high maximum plasma concentration (C). Inhalation is an alternative to intravenous dosing. The surface area of the lung allows for rapid absorption of a self-administered dose.
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March 2024
Quotient Sciences, Miami, Florida, USA.
Objective: To compare the safety and pharmacokinetics (PK) of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), liquid nasal spray (LNS) DHE mesylate, and intramuscular (IM) DHE mesylate injection in healthy participants.
Background: DHE is an effective acute migraine treatment; however, self-administration difficulties have prevented its broader role in the management of migraine.
Methods: This randomized, active-controlled, five-period crossover study was conducted over 5 weeks separated by 1-week washout periods.
Pharmaceut Med
November 2023
Shrewd Consulting LLC, Impel Pharmaceuticals, Seattle, WA, USA.
Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usually the plasma. This is as close to the tissue of interest that we can get, although biopsies may be obtained to give "tissue levels" of drugs.
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