Significantly improved oral uptake of amikacin in FVB mice in the presenceof CRL-1605 copolymer

Amikacin is an aminoglycoside which is used in the treatment of infection f rom gram negative bacteria. Amikacin is also used synergistically with peni cillin against gram positive cocci. Amikacin cannot be delivered orally pro bably due to efflux of drug by P-glycoprotein pump in the brush border of i ntestine. We studied the possibility of delivering amikacin orally in mice using a copolymer (CRL-1605) as a vehicle. This copolymer inhibits beta-gly coprotein pump. Two different doses of amikacin were used (500 mg/kg and 10 0 mg/kg). The concentration of polymer used was 132 mg/kg. The liquid formu lation was fed to mice by gavage and serum amikacin concentrations were est imated after one hour and two hours using flourescence polarization immunoa ssay. We observed a two fold increase in serum amikacin concentration when amikacin was orally delivered in the presence of CRL-1605 compared to contr ols (amikacin alone). We conclude that gastrointestinal absorption of amika cin is significantly increased in the presence of CRL-1605 in mice.