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Online Journal of Veterinary Research ©
Volume 24(12): 699-715, 2020.
Pharmacokinetics and hepatotoxicity of flutamide liposomes after IV administration in Wistar rats
Umrethia ML, Ghosh PK, Majithiya RJ, Murthy RSR.
Drug Delivery Research Laboratory, Pharmacy Department, The M.S. University of Baroda, Vadodara, India
Umrethia ML, Ghosh PK, Majithiya RJ, Murthy RSR., Pharmacokinetics and hepatotoxicity of flutamide liposomes after IV administration in male Wistar rats, Onl J Vet Res., 24(12): 699-715, 2020. Flutamide (FLT) is a non-steroidal anti-androgenic used for treatment of prostate cancer. However, high doses can be hepatotoxic. We encapsulated FLT with stealth liposomes (CL) with normal liposomes (SL) to evaluate pharmacokinetics, reduce uptake and hepatotoxicity. FLT was encapsulated CL with stealth liposome egg phosphotidylcholine (ePC) and cholesterol by thin film hydration followed by high-pressure homogenization. For liposomes, methoxy polyethylene glycol 2000-phosphotidyl ethanolamine (mPEG2000-PE) was added to enhance hydrophilicity. We found that smaller particles (136 nm) with EE of 99.28% were less stable than larger ones (158 nm) with EE of 98.54% in human plasma at 37șC. Encapsulated flutamide was retained 36h whereas free drug or normal liposomes only 2-6h. Plasma half life, Vss, MRT and AUC for FLT was ~2-10 fold higher for stealth liposomes compared with normal liposomes and free drug. Flutamide in all organs was ~75-82% less (P < 0.01) using stealth liposomes compared with free drug or normal liposomes. Histopathological studies and Alanine transaminase (ALT) analysis confirmed that stealth liposomes reduced tioxicity of flutamide in Wistar rats.
Keywords: Flutamide, liposomes, pharmacokinetics, biodistribution, histopathology.