Pharmacokinetics and Pharmacodynamics

Pharmacokinetics and Pharmacodynamics

• 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

• 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

Distribution

• Distribution is the spread of the substance throughout the body.
• The goal of distribution is to achieve the effective drug concentration.
• Factors affecting distribution include:
  • Characteristics of the medication (molecule size, binding capabilities)
  • Patient hydration status
  • Patient plasma protein concentration (albumin can be affected by renal and hepatic function)
  • Patient body condition score
  • Regional blood flow
  • Lipid solubility of the drug
  • Whether the drug becomes protein-bound
  • Physical boundaries (e.g., the blood-brain barrier)

Metabolism

• 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

• 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

Factors Influencing Pharmacokinetics

• 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.

Pharmacokinetics in Practice

• 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.