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.