A
large number of candidate compounds is the basis for drug development, and compound activity
screening and testing are critical to
obtaining candidate compounds with clinical safety data. In screening candidate
compounds, pharmacokinetic parameters are another important screening metric to
examine potential compounds in addition to their efficacy, which can be used to
better control drug development time and reduce drug development costs by
excluding candidates with suboptimal pharmacokinetic parameters early in drug
development.
Modern
advances in science and technology have greatly accelerated the rate of drug
candidate discovery, with thousands of new compounds requiring screening each
year. When a candidate compound enters the clinical phase, it is usually
studied in healthy volunteers to obtain the kinetic parameters of the drug in
humans.
A
large number of candidate compounds are often eliminated for pharmacokinetic
reasons. Important pharmacokinetic parameters such as volume of distribution,
clearance, half-life, and bioavailability determine the extent and duration of
drug exposure in vivo. Early prediction of these parameters in vivo during the
development of new drugs is of great importance for selecting and optimizing
potential candidates.
Some
investigators have used drug transporter evaluation methods, mainly using
cultured cells expressing human drug transporter genes, where the host cell
surface expression protein is also functionally very similar to the human transporter
protein in vivo and thus can be used to provide pharmacokinetic data
approximating clinical trials in the early stages of drug development, to
rapidly screen out candidate compounds that do not have pharmacokinetic
parameters, and thus to The goal is to shorten the development cycle and
minimize unnecessary development costs.
Pharmacokinetic studies are needed better to understand the changes in drugs in the body, to
design and optimize drug delivery, to guide rational drug use, and to provide a
scientific basis for clinical drug use. Medicilon Pharmacokinetics Lab has
passed the GLP certification by NMPA/ NMPA.Following the guiding principles of
ICH, NMPA and FDA. The lab offers in vivo and in vitro pharmacokinetic tests
according to our client's needs and provides them with complete sets of
pharmacokinetic evaluation and optimization services.
There
are many studies to identify candidate compounds by studying their
pharmacokinetic parameters. For example, one researcher used a molecular
docking virtual screening method to construct a natural product library
containing 42,296 small molecules, which were docked to the protein tyrosine
phosphatase 1B (PTP1B) target for the treatment of type II diabetes. The
molecular docking[1] was performed, the binding energy of the original ligand
was used as the threshold value, and the small molecules with scoring values
higher than the threshold value were selected for the prediction of
pharmacokinetic and toxicity parameters after three rounds of screening. Therapeutic
agents.
Some
researchers have also used high-performance liquid chromatography to determine
the concentrations of anthraquinones (aloe-emodin, emodin, rhein, Chrysophanol,and physcion ) in
tissues and plasma[2]. After gavage administration of different preparations,
the pharmacokinetic parameters and distribution characteristics of rhubarb
anthraquinones were studied in rabbits and rats. The results showed that their
elimination processes in rabbits and rats satisfied the two-compartment model.
There
were no statistical differences in the main pharmacokinetic parameters
calculated by the amount of rhubarb acid and total anthraquinone for the
processes in rats. Rhubarb anthraquinones were mainly distributed in the
kidney, liver, heart, and blood and decreased sequentially. Anthraquinones were
present in the body mainly as rhubarb acids and excreted by the kidneys. The
pharmacokinetic study of compound preparations containing rhubarb analogs in
vivo can be carried out using rhubarb acid as an indicator component.
In
the study of active compounds, the final determination of whether they can
become drugs with therapeutic effects is inseparable from their pharmacokinetic
properties and the safety of the drugs. In conclusion, pharmacokinetics plays a
crucial role in the drug development process and is indispensable throughout
the entire process of drug discovery and preclinical and clinical research.
[1]
Virtual screening of natural product-based protein tyrosine phosphatase 1B
inhibitors[J].
[2]
Distribution and pharmacokinetics of five rhubarb anthraquinones in rabbits and
rats[J].
评论
发表评论