What is pharmacokinetics?
- What the body does to the drug
- Refers to the movement of drug into, through and out of the body
- Pharmacokinetics of a drug depends on patient-related factors and the chemical properties of the drug
- There are four components to pharmacokinetics - Absorption, Distribution, Metabolism, and Excretion (ADME)
- Determined by the physiochemical properties, route and formulation of the drug.
- To be absorbed, an orally administered drug must be dissolved in solution and must cross a semi-permeable cell membrane to reach systemic circulation. This is accomplished by passive diffusion, facilitated passive diffusion, active transport and pinocytosis
- Controlled-release oral preparations have the benefit of reduced dosing frequency and may be particularly useful with drugs that have a short half life, allowing a more consistent plasma drug concentration to be achieved. Damaging controlled-release dosage forms prior to administration usually results in undesirable drug degradation and reduced treatment efficacy
- Controlled-release transdermal preparations are also available that allow regular drug absorption over a prolonged period, often up to several days. Drug absorption and adhesion of transdermal patches may be affected by heat, hair etc.
- Drugs given intravenously enter the systemic circulation directly. However, drugs injected intramuscularly or subcutaneously must cross biological membranes to reach the systemic circulation. Tissue perfusion significantly affects capillary absorption of drugs which are administered intramuscularly or subcutaneously. Thus, injection site can have a profound effect on rate of drug absorption
- Volume of distribution - this is the volume of fluid into which the administered drug would be diluted to produce the desired plasma concentration
- For example, if 400mg of drug is administered to a patient and the plasma concentration is 4 mg/L, the volume of distribution is 400 ÷ 4 = 100L
- If a drug is highly tissue bound, plasma drug concentration is low, and volume of distribution is high
- If a drug is not readily tissue bound, plasma drug concentration is hgih, and volume of distribution is low
- Highly lipophilic drugs which are readily partitioned into fat may remain in these tissues for prolonged periods of time because perfusion is poor
- Like tissue binding, the extent of plasma protein binding also significantly affects drug distribution
- It is the unbound, free drug in the plasma that may be partitioned into the target sites and exert its desired pharmacological effect.
- Therefore, the concentration of unbound drug in systemic circulation determines drug efficacy
- Mainly completed in the liver
- Drug metabolism usually inactivates drugs, but some metabolites may be pharmacologically active (sometimes more-so than parent compounds)
- Rate of metabolism varies significantly between individuals, with some patients metabolising a drug very rapidly whilst others may take much longer to metabolise the same drug
- Several factors may affect how quickly a person metabolises a drug, including their genetics, co-morbidities, age, and drug/food interactions
- The most important enzyme involved in drug metabolism is cytochrome P450 (CYP450) which is responsible for the oxidation of many drugs
- CYP450 may be induced or inhibited by drugs and other substances which may subsequently alter the rate of metabolism of other drugs, potentially resulting in reduced drug efficacy on the one hand, or drug toxicity on the other
- Hepatic metabolism of drugs often increases their polarity and makes them more water soluble
- Water-soluble substances are excreted mainly by the kidneys
- Any drug that is not absorbed from the gastro-intestinal tract may be excreted by the biliary system
- Excretion via the sweat, saliva, and breast milk is much less significant