Dose.definition. Types. Therapeutic window (margin) and therapeutic index
A dose is a measured quantity of a medicine, nutrient, or pathogen which is delivered as a unit
- The greater the quantity delivered, the larger the dose
- Characteristics
- There is a relationship between drug effect and drug dose
- Graphically, this dependance is determined by the type of drug effect
- When we have a graded response the effect appears, unfolds, reaches maximum values or becomes toxic
- In alternative drug response we simply register its appearance (e.g. hypnotic, antiepileptic, antiarrhythmic) and the dose-response curve has a bell-shaped look.
- Single drug doses can be:
- Minimal dose- least amount of drug that causes pharmacological effect
- Optimal theraputic dose- dose that shows a beneficial theraputic effect
- Maximal dose- highest theraputic dose that does not lead to toxic effects
- Dosage forms
- Dosage forms are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components
- In general, dosage forms can be present as:
- Solids
- Liquids
- Gases
- Types of doses
- Median effective dose (ED50) - the dose that produces a theraputic effect in 50% of the population that takes it
- Median lethal dose (TD50) - dose needed to kill 50% of members of a tested population
- Theraputic window- difference between the minimal theraputic dose and the minimal toxic dose
- Certain safety factor- ratio of lethal dose to 1% of population to the effective dose to 99% of the population
- Theraputic window (margin)
- Theraputic window- the difference between the minimal toxic and minimal theraputic doses
- Generally, at low concentrations, a drug runs the risk of being ineffective
- At high concentrations, the risk of adverse effects is increased.
- Dosing regimens are designed to maintain drug concentrations within therapeutic windows, maximizing efficacy and minimizing side effects
- Theraputic index ratio between mean lethal + mean effective doses
- Theraputic index- ratio of the dose that produces toxicity in half the population (TD50) to the dose that produces clinically desired response in half the population (ED50)
- TI is a measure of the drug’s safety because a larger value indicates a wide margin between effective and toxic doses
- Examples:
- Warfarin is a drug with a low theraputic index!
- As dose is increased, a greater fraction of patients respond
- At higher doses, anticoagulation resulting in hemorrhage occurs in a small percent of patients
- Penicillin is a drug with a large theraputic index!