Analysis on the Advantages and Disadvantages of Cartridge Drug Delivery

In the development of pharmaceutical preparations, in order to obtain more effective drugs, it is necessary to consider the possible metabolic characteristics and pharmacokinetic parameters of candidate drugs in the process of drug design and screening. Preclinical pharmacokinetic tests are carried out to study the dynamic changes of drugs in animals, to clarify the kinetic processes of drug absorption, distribution, metabolism and excretion, which can provide rich references for subsequent clinical drug trials and clinical rational drug use information. The mouse pharmacokinetic model is a commonly used model for pharmacokinetic research. Some very important pharmacokinetic parameters can be obtained by studying the absorption, distribution, metabolism and excretion of mice after oral administration or injection. The cartridge administration method is a common animal administration method, which can be used for rapid screening of pharmacokinetics in vivo.

In 1997, Berman J et al. proposed a cocktail dosing regimen, also called a cartridge dosing regimen. The main experimental strategy is to mix n drugs and administer them to animals, and at the same time detect the in vivo concentrations of these compounds and calculate their pharmacokinetic parameters. The small animal box-type drug delivery method can comprehensively evaluate the metabolic characteristics of the compound, which has significant advantages in reducing the number of samples, improving throughput and avoiding individual differences.

The determination of pharmacokinetic parameters is of great significance, and has great guiding significance for clinical drug evaluation and pharmacodynamic evaluation. Since mouse physiopathological models are easier to establish than large animals, and mice are easy to obtain materials, mouse pharmacokinetic models are One of the commonly used models for pharmacokinetic research. Some researchers found that in the rapid in vivo evaluation technology, it was established that the whole animal was given multiple drugs at the same time (cartridge administration), and compared with the results of single administration, it was found that the pharmacokinetic parameters of the two administration methods were not obvious. difference. Some researchers also used LC-MS/MS technology to administer cartridge to mice, and simultaneously determined the pharmacokinetic properties of four sEH inhibitors. The amount of whole blood was only 5μl, which was compared with subcutaneous or intraperitoneal injection alone. The pharmacokinetic parameters peak time, plasma peak concentration and half-life value are similar. It not only greatly improves the speed of data collection, but also greatly reduces the cost and the number of animals used, which is suitable for high-throughput pharmacokinetic screening research.

In the development of pharmaceutical preparations, clarify the kinetic characteristics of the process of drug absorption, distribution, metabolism and excretion, and provide important kinetic parameters based on mathematical models to preliminarily judge whether the drug is necessary for further development and research, and preliminary screening leads The compounds provide very important reference materials for pharmacology, toxicology, pharmacodynamics and clinical trials as well as for guiding clinical medication. Medicilon can provide customers with high-quality pharmacokinetic services from all small molecules to large molecules (proteins and antibodies), including in vitro ADME and in vivo pharmacokinetics and biological analysis. The animal species involved are non-human primates, dogs, mice, rats, rabbits, guinea pigs, etc. Among them, the non-primate platform and the isotope protein/antibody experimental platform were recognized as important laboratory platforms by the Shanghai Municipal Government.

The box-type administration method needs to consider how the drugs contained in each group of experiments are combined, and it is most suitable for the administration and testing of this group of drugs. In terms of administration, drugs with the same or similar physical and chemical properties are required to be placed in a group to facilitate the dissolution and administration of the group of drugs and reduce the difficulty of exploring HPLC conditions. The cartridge drug delivery method has advantages in saving experimental resources and increasing throughput. Firstly, due to the reduction in the number of samples, the analysis time is also significantly shortened, thereby increasing the throughput; secondly, because several drugs are given to a test animal at the same time, it can Reduce the individual differences of animals, sometimes the individual differences of animals will cause the distortion of the trend; in addition, the amount of animals can be reduced.

When choosing a cartridge dosing regimen for determination, it is necessary to detect multiple compounds in a single sample at the same time, so it is necessary to establish a highly selective method. At the same time, in order to avoid interaction, reduce toxicity, and reduce risk, a relatively low dose is required after multiple compounds are mixed, so the analytical method needs to have high sensitivity.

Moreover, after multiple chemical substances are administered to an animal, compound interactions may occur. These interactions may competitively inhibit the binding of drug metabolizing enzymes, transporters, and plasma proteins, and may lead to false negative and false positive results, thereby affecting the pharmacokinetics. Determination of scientific properties. In this case, it is necessary to reduce the dosage to avoid possible intra-group drug enzyme inhibition or to add a reference compound to minimize this interaction. Due to the existence of interaction, cartridge administration can only make the pharmacokinetic parameters better than that of single administration. Therefore, it will not miss the selection in the crude drug selection, and further screening will eliminate the misselected compound.

It can be seen that the cartridge dosing method will increase the difficulty of the analysis method and increase the possibility of drug-drug interaction. Therefore, evaluation and verification are needed to establish an appropriate cartridge dosing analysis method.