In Vivo Pharmacokinetics Evaluation of Cardiovascular Drugs

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Before a drug is administered to humans for the first time, it is imperative to evaluate its pharmacokinetic properties through animal studies. Ace Therapeutics has a proven preclinical technology platform to help clients conduct in vivo pharmacokinetic studies for cardiovascular drugs.

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Animal Models for In Vivo Pharmacokinetics Evaluation

For non-clinical pharmacokinetic studies, it is best to choose animals with clear genetic background and similar metabolic processes to humans. Young, old, pregnant, disease model animals can be used to study the pharmacokinetic law of different age, physiology, pathological state, without special requirements, generally choose adult, healthy animals. The general principles of experimental animal selection are as follows.

• Preferred experimental animals are consistent with the pharmacodynamics and toxicology studies.
• The experimental animals can meet the needs of multiple sampling
• Innovative cardiovascular drugs should use two or more kinds of experimental animals (one of which is rodent, one of which is non-rodent) to carry out pharmacokinetic studies.

Fig. 1 Large animal models of HFrEF divided into surgical and endovascular methods. (Spannbauer A, et al., 2019)

Ace Therapeutics can provide comprehensive in vivo pharmacokinetic studies for different types of cardiovascular drugs.

Available Animal Models for Pharmacokinetics Evaluation

Depending on the clinically intended characteristics of the cardiovascular drug to be evaluated, we can use commonly available and common healthy experimental animals as well as in specific animal models of cardiovascular disease used as pharmacokinetic evaluations in pathological states.

Commonly Used Animal Models

• Mouse Models (C57BL/6 mice, BALB/c mice)
• Rat Models (SD rats, Wistar rats)
• Rabbit Models (New Zealand white rabbits, Japanese white rabbits)
• Monkey Models (Rhesus macaques, Cynomolgus macaques)
• Pig Models (Obbassaw mini-pigs, Rapacz pigs)

Animal Models of Cardiovascular Diseases

• Animal Models of Atherosclerosis
• Animal Models of Hypertension
• Animal Models of Thrombosis
• Animal Models of Myocardial Ischemia/Infarction
• Animal Models of Arrhythmia
• Animal Models of Heart Failure
• Animal Models of Hypertrophic Cardiomyopathy
• Animal Models of Heart Valve Disease
• Animal Models of Cardiovascular Infection

Dose Selection

The in vivo pharmacokinetic study in animals should be set up with at least three dose groups, whose high doses are preferably close to the maximum tolerated dose, and the medium and small doses are selected according to the upper and lower ranges of the effective dose in animals. It is mainly examined whether the in vivo kinetic process of the drug is linear or nonlinear within the range of doses tried, in order to facilitate the interpretation of the findings in pharmacodynamic and toxicological studies, and to provide information for further development and research of new drugs.

Statistical Analysis of Pharmacokinetic Data

We can comprehensively analyze and evaluate the obtained experimental data, calculate the main pharmacokinetic parameters of the tested cardiovascular drugs, and comprehensively determine the pharmacokinetic (ADME process) characteristics of the drugs in animals.

• Peak Time (T_max)
• Peak Concentration (C_max)
• Area Under Curve (AUC)
• Terminal Elimination Half-life (T_1/2)
• Bioavailability (F)
• Apparent Volume of Distribution (Vd)
• Elimination Rate Constant (Kel)

Ace Therapeutics is a contract research organization specializing in drug research for cardiovascular diseases. With our specialized equipment platform and dedicated research team, we can provide in vivo pharmacokinetic studies of cardiovascular drugs according to the needs of our clients. If you are interested in our services, please don't hesitate to contact us.

1. Spannbauer, A.; et al. Large animal models of heart failure with reduced ejection fraction (HFrEF). Front Cardiovasc Med. 2019, 6:117.