TY - JOUR T1 - Pharmacokinetics of long-term low-dose oral rapamycin in four healthy middle-aged companion dogs JF - bioRxiv DO - 10.1101/2021.01.20.427425 SP - 2021.01.20.427425 AU - Jeremy B. Evans AU - Ashley J Morrison AU - Martin A. Javors AU - Marisa Lopez-Cruzan AU - Daniel E.L. Promislow AU - Matt Kaeberlein AU - Kate E. Creevy Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/20/2021.01.20.427425.abstract N2 - Objective To determine the blood concentration and pharmacokinetic parameters of rapamycin in companion dogs following long-term, low-dose oral administration of rapamycin.Animals Four healthy, middle-aged, medium-to-large breed privately owned dogs participated.Procedures All dogs had been receiving oral rapamycin at a dose of 0.025 mg/kg on Monday, Wednesday, and Friday mornings for at least one month. An initial blood sample was collected prior to morning rapamycin administration, and samples were collected at 1, 2, 6, and 24 hours after rapamycin was given. Blood samples were transferred to blood spot collection cards, air-dried and stored at −80°C. Rapamycin concentrations were determined via HPLC/MS. All blood collections occurred on Wednesdays, so that the previous dose of rapamycin had taken place 48 hours prior to blood collection.Results For all dogs, rapamycin Tmax was 2 hours. Median Cmax was 1.47 ng/ml (0.912 – 2.13), and the median AUC0-last was 15.7 ng*hr/mL (1.30 – 36.3). Due to sample size and timing, the only estimates related to elimination rate reported are for mean residence time with a median of 4.70 hrs (0.90 – 7.30).Conclusions and Clinical Relevance A 0.025 mg/kg oral dose of rapamycin, administered three times a week, resulted in concentrations of rapamycin in the blood capable of being measured in ng/ml.HPLC/MS/MSHigh performance liquid chromatography – mass spectroscopy ER -