Bioequivalence Study of Selected Ketoconazole Drug Products
Keywords:
Bioequivalence, Ketoconazole, Pharmacokinetics, Generic drugs, HPLC, Therapeutic equivalenceAbstract
Ketoconazole is a broad-spectrum antifungal agent used in the management of systemic and superficial fungal infections. Its poor solubility and variable gastrointestinal absorption and differences in formulation may significantly influence bioavailability. Ensuring therapeutic equivalence of generic ketoconazole formulations is therefore critical to guarantee clinical efficacy and safety. This study aimed to evaluate the bioequivalence of selected ketoconazole drug products available in the market, using standard pharmacokinetic and statistical approaches.
A randomized, two-period, two-sequence crossover design was employed in healthy adult participants under fasting conditions. Each subject received a single oral dose of the reference ketoconazole product and one of the test formulations, with a suitable washout period between administrations. Blood samples were collected at predetermined intervals, and plasma ketoconazole concentrations were quantified using validated high-performance liquid chromatography (HPLC) methods.
Pharmacokinetic parameters including maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and area under the plasma concentration-time curve (AUC₀–t and AUC₀–∞) were calculated. Statistical analysis was performed to assess the 90% confidence intervals for the log-transformed ratios of Cmax and AUC values. Mean pharmacokinetic profiles of the test and reference products were comparable. The 90% confidence intervals for the ratios of Cmax, AUC₀–t, and AUC₀–∞ fell within the accepted regulatory range of 80–125%, confirming bioequivalence.
The selected ketoconazole drug products demonstrated bioequivalence to the reference formulation, indicating therapeutic interchangeability. These findings support the continued use of approved generic ketoconazole formulations in clinical practice, thereby enhancing accessibility and reducing treatment costs without compromising efficacy.
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