Comparative pharmacokinetics of free doxorubicin and a liposomal formulation in cats following intravenous administration

Doxorubicin, a potent chemotherapeutic agent used extensively in cancer treatment, displays complex pharmacokinetic behavior, especially across various formulations. With a rising incidence of cancer cases in cats, understanding the drug's pharmacokinetics in feline subjects remains a critical yet unexplored area. Hence, this study investigated the pharmacokinetic profile of doxorubicin after slow intravenous administration of doxorubicin hydrochloride (DOX center dot HCl) or doxorubicin hydrochloride pegylated liposome (DOX center dot HCl-PLI) in twelve cats at a single dose of 20 mg/m2. Blood samples collected at pretreatment time (0 h) and over 192 h were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The obtained pharmacokinetic parameters of doxorubicin revealed significant differences between the two formulations and were as follows: elimination half-life (T1/2 lambda z) of 5.00 +/- 3.20 h (DOX center dot HCl) and 17.62 +/- 8.13 h (DOX center dot HCl-PLI), area under the concentration/time curve from 0 to last point (AUClast) of 0.67 +/- 0.12 mu g hr./mL (DOX center dot HCl) and 783.09 +/- 267.29 mu g hr./mL (DOX center dot HCl-PLI), and total body clearance (CL_obs) of 27098.58 +/- 5205.19 mL/h/m2 (DOX center dot HCl) and 28.65 +/- 11.09 mL/h/m2 (DOX center dot HCl-PLI). Additionally, differences were also detected in the apparent volume of distribution (Vz_obs) with 178.56 +/- 71.89 L/m2 (DOX center dot HCl) and 0.64 +/- 0.20 L/m2 (DOX center dot HCl-PLI), and the maximum plasma concentration (Cmax) with 2.25 +/- 0.30 mu g/mL (DOX center dot HCl) and 24.02 +/- 5.45 mu g/mL (DOX center dot HCl-PLI). Notably, low concentration of doxorubicinol, the metabolite of doxorubicin, was detected in plasma after administration of DOX center dot HCl, with even less present when DOX center dot HCl-PLI was administered. This investigation provides valuable insights into the distinct pharmacokinetic behaviors of DOX center dot HCl and DOX center dot HCl-PLI in cats, contributing essential groundwork for future studies and potential clinical applications in feline oncology.