Salient pharmacological features:
This drug is widely distributed in the body, predominantly in bladder, kidneys, liver, prostate gland, salivary gland (mandibular), pancreas, seminal vesicle, epididymis and testes. It is administered via intravenous route. Half life of the drug is 0.84-1.04 hr. It gets elimintated majorly by renal (63%) and billiary excretion (27.8%). It poorly crosses blood-brain barrier. Remdesivir is partially metabolized by the cytochrome P450 enzymes CYP2C8, 2D6, and 3A4.[17] Pharmacokinetic experiments in cynomolgus monkeys demonstrated low bioavailability of the drug. Intramuscular injection of 3 mg/kg had a 50% survival rate compared with the control group. Intravenous administration at a dose of 10 mg/kg got rapidly converted into nucleoside phosphate in rhesus monkeys. Within 2 hr, remdesivir quickly gets distributed in peripheral blood mononuclear cells (PBMCs), and soon afterwards activated to nucleoside triphosphate to reach a peak, with a survival rate of 100%.[18] Pharmacokinetic studies performed in vivo showed after the intravenous infusion at a single dose of 3–225 mg for 2 h, it showed dose-linear pharmacokinetics. In the case of daily administration, the active substance of the drug will be accumulated in vivo. As a result, in large-scale clinical trials, after the first dose of 200 mg is administered, the subsequent dose is adjusted to 100 mg to ensure the proper blood concentration in vivo.[19]Intravenous infusions in previously phase I clinical trials have good safety and pharmacokinetic properties without any cytotoxicity, hepatorenal toxicity, or no serious adverse reactions.