Pharmacokinetics evaluation of newly formulated beads alginate/gum acacia loaded ketoconazole in rabbit plasma by oral administration

• Published in: ADMET & DMPK 2024-01, Vol.12 (2), p.335-341
• Main Authors: Annisa, Viviane, Sulaiman, Teuku Nanda Saifullah, Nugroho, Akhmad Kharis, Nugroho, Agung Endro
• Format: Article
• Language: English
• Subjects: bioavailability; drug; hydrogel; in vivo; Original Scientific Paper; polymer
• ISSN: 1848-7718; 1848-7718
• DOI: 10.5599/admet.2042

The combination of alginate and gum acacia in previous studies showed good results in inhibiting ketoconazole precipitation due to the supersaturation phenomenon. Ketoconazole-loaded alginate and gum acacia can produce hydrogel beads through cross-linking with Ca using ionotropic gelation techniques. However, the pharmacokinetic study of the ketoconazole beads loaded to alginate and gum acacia needs further investigation. This study aimed to evaluate pharmacokinetic parameters using rabbits via oral administration. The drug was administered orally to 2 groups of rabbits: pure ketoconazole (KTZ) and formulation of ketoconazole (AG75) groups. Blood samples were obtained from the ear marginal vein at various time points: 0 (before administration), 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360, and 420 minutes after oral dosage. The pharmacokinetic study employed a non-compartment analysis to calculate the area under the curve (AUC), the volume of distribution ( ), clearance ( ), maximum concentration ( ), and time to reach maximum concentration ( ). The data obtained from the parameter result was analyzed using the independent-sample T-test. The results of the KTZ group include AUC of 15.83±0.62 h μg mL , of 8.95±1.17 mL, of 3.45±0.3 mL h , of 4.7±0.69 μg mL , and of 1.67±0.17 h. The results of the AG75 group include AUC of 27.8±1.01 h μg mL , of 11.5±2.4 mL, of 2.15±0.11 mL h , of 4.49±0.52 μg mL , and of 2.5±0.5 h. The formulation incorporating ketoconazole beads resulted in a higher AUC than the pure ketoconazole. This finding suggests that the created formulation has enhanced the bioavailability of ketoconazole.