Bioavailability of tobramycin after oral delivery in FVB mice using CRL-1605 copolymer, an inhibitor of P-glycoprotein

Tobramycin is an aminoglycoside used in the treatment of infection against gram-negative bacteria. Tobramycin cannot be delivered orally probably due to efflux of drug by a P-glycoprotein pump in the brush border of the small intestine, In this report we demonstrate oral delivery of tobramycin in FV B mice using CRL-1605 copolymer as a vehicle. This copolymer is known to in hibit P-glycoprotein. Two different doses of tobramycin (25 mg/kg and 200 m g/kg) were used. The concentration of CRL-1605 copolymer was 132 mg/kg, The liquid formulation was fed to mice by gavage and serum tobramycin concentr ations were measured after one and two hours using the fluorescence polariz ation immunoassay. We observed significant increases in serum tobramycin co ncentrations when the drug was delivered orally with the copolymer compared to when the drug was delivered alone. We also performed a bioassay using B acillus subtilis to confirm antibacterial effect of tobramycin in mice sera . This was to ensure that tobramycin did not undergo structural change duri ng oral absorption when delivered in the copolymer vehicle, We observed min imal inhibition in growth of Bacillus subtilis in sera obtained from mice f ed with tobramycin alone, In contrast, we observed almost complete inhibiti on of growth (most specimens) in sera obtained from mice fed with tobramyci n in the presence of CRL-1605 copolymer. We conclude that tobramycin delive red orally in mice using copolymer 1605 is also bioactive, (C) 2000 Elsevie r Science Inc, All rights reserved.