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The most important property of a dosage of a drug administration is its ability to deliver the active ingredient to the site of action in a quantity sufficient to exert the expected pharmacological effect. This ability is known as bioavailability. Dexamethasone is a drug with wide clinical use in patients with inflammatory pathologies (infectious or non-infectious). The main routes of administration are oral and intravenous. The intranasal route could be one more effective, less invasive that would allow to obtain a faster therapeutic concentration and in greater concentration in the lungs and in the central nervous system than the intravenous route, maintaining very similar systemic concentrations to those achieved intravenously. For these reasons, it is important to know the bioavailability of dexamethasone administered by this route in order to establish the best dosing regimen. The pilot study is of an exploratory nature (descriptive, comparative or informative), whose objective is to know the pharmacokinetic characteristics of a new route of administration of a drug in the study population to establish the pharmacokinetic parameters, and the comparison between the intranasal bioavailability against the intravenous administration by determining confidence intervals and calculating one-sided double t of Scuirmann.
Objetive: To evaluate the Absolute Bioavailability (for information purposes) of Dexamethasone 8 mg/2 ml Injectable Solution (Intranasal Route 6 mg/ 1.5 ml Vs Intravenous Route 6 mg/ 1.5 ml), according to the specific evaluation parameters and general under fasting conditions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenously DMX | Active Comparator | Male and female volunteers received one dose of DXM. Drugs formulations employed were DXM phosphate injectable solution 8 mg/2 mL (Alin, Productos Farmaceuticos, Mexico). The drug was administered to 4 subjects intravenously (treatment A) according to a randomization list generated prior to the start of the clinical phase. |
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| Intranasally DMX | Active Comparator | Male and female volunteers received one dose of either DXM Drugs formulations employed were DXM phosphate injectable solution 8 mg/2 mL (Alin, Productos Farmaceuticos, Mexico). The drug was administered to 4 healthy subjects intranasally (treatment B). According to a randomization list generated prior to the start of the clinical phase. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexamethasone | Drug | The nominal doses were similar, volunteers were randomly assigned to receive a single dose of DXM by IV bolus of 1.5 mL (equivalent to 6 mg of dexamethasone) or the same dose intranasally by using a Mucosal Atomization Device (MAD Nasal). allowing direct pharmacokinetic comparison without dose normalization. Venous blood samples were obtained via an indwelling catheter before administration and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12 and 24 h for DXM. Plasma was separated and frozen at -70 °C for further analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Bioavailability of Dexamethasone (6 mg/ 1.5 mL Intranasal Route vs. 6 mg/ 1.5 mL Intravenous Route) | The sample size used for this exploratory study (descriptive, comparative or informative) made it possible to determine the absolute bioavailability (with informative value), for which the bioavailability was compared in the 2 types of administration: Intranasal vs. Intravenous with a sample size of 8 research subjects, even though the ANADEVA is informative, the requirements regarding type I error (alpha), type II error (beta) and a minimum difference to detect between the 2 routes of administration: intranasal vs. IV. The realization of the present study allowed to know the pharmacokinetic and safety parameters of the drug Alin® administered by 2 different routes, as well as to determine the CVintra%. | 2 weeks |
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Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible to participate in the study:
Exclusion Criteria:
Subjects presenting any of the following circumstances will not be included in the study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universidad Nacional Autonoma de Mexico | Mexico City | 04510 | Mexico |
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| ID | Term |
|---|---|
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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2 PERIODS, 2 TREATMENTS, 2 SEQUENCES, CROSSOVER 2X2.
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|
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |