Pilot Study to Evaluate Bioavailability of Methylprednisolone Administered Intranasally.

Pilot Study to Evaluate the Absolute Bioavailability of Methylprednisolone Succinate Administered Intranasally

The most important property of a drug dosage 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. Methylprednisolone 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 andin 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 methylprednisolone 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 of methylprednisolone in healthy subjects of both genders, with administration. intranasally vs. intravenous dose of 1 ml of methylprednisolone sodium succinate equivalent to 62.5 mg of methylprednisolone.

Study Overview

• Status: Completed
• Conditions: Bioavailability of Methylprednisolone Intranasally; Bioavailability of Methylprednisolone Intravenously; Comparison Intranasally vs Intravenously
• Intervention / Treatment: Drug: Evaluation of bioavailability of methylprednisolone succinate administered intranasally

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 04510
    • Universidad Nacional Autonoma de Mexico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age between 18 and 55 years. Clinically healthy. Body mass index between 18.0 and 27.0 Kg/m2. Negative results to detect the presence of human immunodeficiency virus [HIV], Hepatitis B [HBV], Hepatitis C [HCV) and test for detection of Syphilis (VDRL).

Subjects with negative results in tests for the detection of drugs of abuse such as: amphetamines, benzodiazepines, cocaine, methamphetamines, morphine and tetrahydro-cannabinoids.

Negative (qualitative) pregnancy test.

Exclusion Criteria:

Subjects with any condition or alteration of the nose or nasal mucosa. Subjects with a history of hypersensitivity to the study drug. Subjects with a history of cardiovascular, renal, hepatic, metabolic, gastrointestinal, neurological, endocrine, hematopoietic disorders (any type of anemia), mental illness or other organic abnormalities that could affect the pharmacokinetic study of the product under study.

Subjects who require any medication during the course of the study. Principal Investigator will not include the subject in the study. Subjects who have been hospitalized for any reason within the sixty days prior to the start of the study or who have been seriously ill within the thirty days prior to the start of the study.

Subjects who have received an investigational drug within ninety days prior to the start of the study.

Subjects who have donated or lost 450 ml or more of blood within the ninety days prior to the start of the study.

Subjects who have smoked tobacco, ingested alcohol, consumed beverages or foods containing xanthines.

Positive (qualitative) pregnancy test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenously MEP; Single dose of MEP sodium succinate intravenously administered. MEP (equivalent to 62.5 mg of Methylprednisolone). Samples were obtained at 0.333, 0.50, 0.667, 0.833, 1, 1.0, 2, 3, 4, 6, 8, 10, 12 and 24 h after MEP administration.	Drug: Evaluation of bioavailability of methylprednisolone succinate administered intranasally; Bioavailability of methylprednisolone in healthy subjects of both genders, was conducted comparing intranasal administration vs intravenous.
Active Comparator: Intranasally MEP; Volunteers were randomly assigned to receive a single dose of MEP intranasally administered (equivalent to 62.5 mg of Methylprednisolone), using a Mucosal Atomization Device (MAD Nasal). Samples were obtained at 0.333, 0.50, 0.667, 0.833, 1, 1.0, 2, 3, 4, 6, 8, 10, 12 and 24 h after MEP administration.	Drug: Evaluation of bioavailability of methylprednisolone succinate administered intranasally; Bioavailability of methylprednisolone in healthy subjects of both genders, was conducted comparing intranasal administration vs intravenous.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics assessment of MEP intranasally administered	MEP concentrations in plasma were determined by reverse liquid chromatog-raphy and detected by tandem mass spectrometry (LC-MS/ MS). Analysis of samples was performed using an HPLC system Agilent G1312C coupled with a turbo ion spray ionization-triple quadrupole mass spectrometer Agilent G6410B, with negative ion electrospray ionization using MRM mode. Briefly, to 100 µL of plasma sample, 400 µL of acetonitrile were added. After vortex mixing for 4 min, samples were centrifuged. The supernatant was separated and 10 µL were injected into the chromatographic sys-tem. Separation was achieved using a Zorbax Eclipse Plus ® (Agilent) C18 column (3.5 μm, 100 mm x 4.6 i.d.). The mobile phase was composed of methanol HPLC ammoni-um formate 2.5mM in water (90:10 v/v) at a flow rate of 0.8 mL/min.	2 weeks
Pharmacokinetics assessment of MEP intravenously administered	MEP concentrations in plasma were determined by reverse liquid chromatog-raphy and detected by tandem mass spectrometry (LC-MS/ MS). Analysis of samples was performed using an HPLC system Agilent G1312C coupled with a turbo ion spray ionization-triple quadrupole mass spectrometer Agilent G6410B, with negative ion electrospray ionization using MRM mode. Briefly, to 100 µL of plasma sample, 400 µL of acetonitrile were added. After vortex mixing for 4 min, samples were centrifuged. The supernatant was separated and 10 µL were injected into the chromatographic sys-tem. Separation was achieved using a Zorbax Eclipse Plus ® (Agilent) C18 column (3.5 μm, 100 mm x 4.6 i.d.). The mobile phase was composed of methanol HPLC ammoni-um formate 2.5mM in water (90:10 v/v) at a flow rate of 0.8 mL/min.	2 weeks

Collaborators and Investigators

• Sponsor: Edda Sciutto Conde

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2021
• Primary Completion (Actual): November 10, 2021
• Study Completion (Actual): November 12, 2021

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: pharmacokinetics; intranasal; Bioavailability; methylprednisolone
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: BE-PNO-049-F01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No