A replicate study design for testing bioequivalence: a case study on two desmopressin nasal spray preparations

Area of Science:

• Pharmacokinetics and Bioequivalence Studies
• Drug Formulation and Delivery

Background:

• Intranasally administered peptides, such as desmopressin, exhibit high plasma pharmacokinetic variability.
• Appropriate study designs are crucial for accurately assessing bioequivalence of nasal spray formulations.

Purpose of the Study:

• To evaluate the bioequivalence of a test desmopressin nasal spray preparation against a reference product.
• To confirm that the rate and extent of drug absorption are comparable between the two formulations.

Main Methods:

• A single-dose, replicate study design was employed with 32 healthy male volunteers.
• A 4-period, 2-sequence crossover design was used, with subjects receiving 20 microg desmopressin-acetate per dose.
• Serial blood concentrations were measured over 14 hours using radioimmunoassay, with statistical analysis via mixed analysis of variance.

Main Results:

• The test and reference desmopressin nasal sprays demonstrated comparable pharmacokinetic profiles.
• Mean test/reference ratios for AUC(0-14 h), C(max), and t(max) fell within the bioequivalence range (0.80-1.25).
• Specifically, ratios were 1.041 (AUC), 1.021 (Cmax), and 1.068 (tmax), all with 90% confidence intervals within the acceptance range.

Conclusions:

• The desmopressin test preparation is bioequivalent to the reference nasal spray.
• Both preparations exhibit identical rates and extents of intranasal desmopressin absorption.
• The study confirms the interchangeability of the tested desmopressin nasal spray formulations.