Teklad global diet 2014

Male CD1 mice on Teklad Global Diet 2014 (Envigo Teklad, Madison, WI) (n = 2–3 per study) received a single IV, oral or intraperitoneal (IP) administration of compounds 1, 4, 5 or 6 at 1 mg/kg in 2:5:20:73 (v/v) DMSO:Tween 80:PEG-400:D5W dosed at 10 ml/kg. Serial blood samples were taken over 24h and frozen at −20°C until analysis. Pharmacokinetic parameters after IP or PO dosing were calculated by noncompartmental methods, while pharmacokinetic parameters after IV dosing were calculated by compartmental methods using WinNonlin (version 5.2, Certara USA Inc., St. Louis, MO). Mean parameters were determined from 1–3 separate studies. FaFg was determined as F/F_h (compound 6) or as the ratio of AUC after an oral dose to that after an IP dose (AUC_oral/AUC_ip).

Active Parent–Male CD1 mice (N = 3) received a single oral administration of compound 1 at 30 mg/kg prepared as a nanosuspension in 2% HPC-SL, 0.2% SDS in water and dosed at 10 ml/kg. Active Parent Prodrugs–Male CD1 mice or female C57BL/6 mice (N = 3) received a single oral adminstration of prodrug at 30 mg/kg active parent equivalent in either 10% Cremophor EL + 90% 1% Na-carboxymethylcellulose (NaCMC) at 10 ml/kg or as a nanosuspension in 2% HPC-SL, 0.2% SDS in water at 10 ml/kg.Blood samples were taken over 11 hours, and colon samples were taken at 3, 6 and/or 11 hours post dose. Mice received either Teklad Global Diet 2014 (Envigo Teklad, Madison, WI or LabDiet #5010 (LabDiet, St. Louis, MO).

Wistar breed rats of the Rattus novergicus species were used in our experiment
according to Spanish legal requirements
(RD 53/2013), the bioethics committee of the University of Extremadura
(137-2020), and approval of the Board of Extremadura (EXP20200904).
The design and performance of the experiment, including animal manipulation
and euthanasia, were carried out by licensed veterinarians with all
requirements by legal authority (Dirección General de Sanidad
Animal de Junta de Extremadura). Twelve male rats were used in the
present study. The rats were supplied and maintained during the whole
assay at the Animal Facilities Service of the University of Extremadura
(Cáceres, Spain), and at the beginning of the assay, they were
6–7 weeks old and weighed 186 g on average. During the entire
study period, the same rodent basal feed used was the “Teklad
Global Diet 2014”, supplied by ENVIGO (Madison, WI), with a
crude protein content of 14.3%.