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Published on: May 9, 2025
Comparative Bioavailability of Two Formulations of Biopharmaceutical Classification System (BCS) Class IV Drugs: A
Ahmed M Saeed1, Jeffery M Schmidt2, Wijith P Munasinghe3
1Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, IL, USA.
Background:
Lopinavir/ritonavir (LPV/r-A, Kaletra®), a fixed dose, co-formulated antiviral therapy for the treatment of HIV infection has been used worldwide for over two decades. Both active substances have low solubility in water and low membrane permeability. LPV/r-A tablets contain key excipients critical to ensuring acceptable bioavailability of lopinavir and ritonavir in humans. An established dog pharmacokinetic model demonstrated several generic LPV/r tablet formulations have significant oral bioavailability variability compared to LPV/r-A.
Methods:
Analytical characterizations of LPV/r-B tablets were performed and a clinical study was conducted to assess the relative bioavailability of Kalidavir® (LPV/r-B) 400/100 mg tablets relative to Kaletra® (LPV/r-A) 400/100 mg tablets under fasting conditions.
Results:
The presence of active substances were confirmed in LPV/r-B tablets in an apparent amorphous state at essentially the labeled amounts, and dissolution profiles were generally similar to LPV/r-A tablets. Excipients in the tablet formulation were found to be variable and deviate from the labeled composition. Lopinavir and ritonavir exposures (AUC) following LPV/r-B administration were approximately 90% and 20% lower compared to that of LPV/r-A.
Conclusions:
LPV/r-B was not shown to be bioequivalent to LPV/r-A.
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