Comparative Bioavailability of Two Formulations of Biopharmaceutical Classification System (BCS) Class IV Drugs: A Case Study of Lopinavir/Ritonavir.
J Pharm Sci
; 110(12): 3963-3968, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34530003
ABSTRACT
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Productos Biológicos
/
Infecciones por VIH
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Inhibidores de la Proteasa del VIH
/
Fármacos Anti-VIH
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article