3.7. In Vivo Pharmacokinetic Study

Adult male Sprague Dawley (SD) rats were used with an average weight of 230 ± 23 g. The animals were accommodated at the animal facility of the University of Petra Pharmaceutical Center (Amman, Jordan) under a controlled temperature (22–24 °C), humidity (55–65%), and a 12 h light/dark photoperiod cycle. The rats were offered clean tap water ad libitum and fed with a standard pellet diet (Jordan Feed Co. Ltd., Amman, Jordan). The rats were randomized into groups and acclimatized for 10 days before experimentation.

The rats were randomized, weighed, and tail marked into two groups, namely a capmatinib-administered group and a placebo group (n = 6). The capmatinib was freshly dissolved in a 0.5% carboxymethylcellulose (CMC) solution prepared in distilled water while the placebo solution consisted of 0.5% CMC alone. The fasting rats (12 h, water ad libitum) were administered either capmatinib at 10 mg/kg dose or an equivalent amount of 0.5% CMC solution by oral gavage using a stainless-steel oral gavage needle (Harvard Apparatus, Holliston, USA).

A volume of 200 µL of the blood samples was obtained from the retro-orbital plexus using clean capillary tubes and collected into Minicollect EDTA tubes. Blood sampling was performed under light isoflurane anesthesia (Hikma Pharmaceuticals, Amman, Jordan) (5% induction and 2.5% maintenance) carried by oxygen (dual-flow oxygen concentrator, China) using a low-flow anesthesia system (SomnoSuite, Kent Scientific, Torrington, CT, USA). An initial blood sample, a zero-time sample, was collected from each animal. The blood samples were then collected at specific time intervals at 0.25, 0.50, 1, 2, 4, 8, and 24 h post-drug administration. The collected blood tubes were centrifuged for 10 min at 6000 rpm using a Hettich EBA 20 centrifuge, Tuttlingen, Germany. The clear plasma samples were then collected and stored at −80 °C until HPLC analysis.

The PKSolver [24] was used to perform a non-compartmental pharmacokinetics analysis.