Pharmacokinetics and Pharmacodynamics

Study Notes

Pharmacokinetics refers to the movement of drugs into, through, and out of the body.
It is divided into four stages: absorption, distribution, metabolism, and excretion.

Absorption is the journey of the drug from administration into systemic circulation.
It affects the speed and concentration of the drug reaching its location of effect.
Bioavailability refers to the fraction of an administered dose of unchanged drug that reaches systemic circulation.
Factors affecting absorption include:
- Form of the drug (e.g., aqueous solutions are more rapidly absorbed than oily solutions, suspensions, or solids)
- Route of administration (no absorption for IV administrations)
- Physical and chemical characteristics of the drug
- Blood flow at the administration site

Metabolism is the conversion of drugs to make them more soluble for excretion.
The majority of drug metabolism occurs in the liver.
The health of the liver can significantly impact the efficacy of medicines and the risk of toxicity.
Factors affecting metabolism include:
- Liver enzymes (e.g., CYP450)
- Enzyme inducers (e.g., phenobarbital and rifampicin) increase the number of cytochrome enzymes, increasing the rate of drug metabolism
- Enzyme inhibitors (e.g., cimetidine, diltiazem) reduce the number of cytochrome enzymes, decreasing the rate of drug metabolism
- Hepatic dysfunction and the neonatal and geriatric life stages are likely to display a reduced ability of the liver to cope with medication

Excretion is the lowering of plasma drug concentration through clearance.
Clearance is achieved by excretion of unaltered drug or metabolism followed by excretion.
The principle organ involved in excretion is the kidney, which removes water-soluble material from the body.
Factors affecting excretion include:
- Renal disease may reduce the body's ability to excrete metabolites or the unchanged drug
- Patients with renal dysfunction may require reduced doses or certain medications being avoided entirely

Species: Cats have much slower hepatic drug metabolism than many other species.
Age: Fetal, newborn, and geriatric animals have limited/reduced capacity to metabolize drugs.
Sex: In rats, females metabolize drugs more slowly than males.
Weight/body condition: Additional fat tissue results in increased distribution space, lowering serum concentrations of fat-soluble medications.
Underlying medical conditions: Hydration/excretory system function, renal disease, hepatic disease, and circulatory disease/shock can impact pharmacokinetics.

Each individual is likely to respond to medication in a slightly different way, requiring dose adjustments to suit the patient.
A good understanding of pharmacokinetics and its impact can help vets select suitable doses and methods of administration.
This is the principle behind therapeutic drug monitoring.