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Pharmacy Practice

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PHAR6113 – Pharmacokinetics
Lecture 2 – Therapeutic Drug Monitoring
Therapeutic Range
• The range at which a drug is achieving a desired response and minimal adverse effects
• The intention in clinical practice is to maintain plasma drug concentrations within this range
• A drug with a narrow therapeutic index is one that has a narrow range between toxic and ineffective concentrations Therapeutic Drug Monitoring (TDM)
• Therapeutic drug monitoring is the clinical practice of measuring specific drugs at designated levels to maintain a constant concentration in a patient’s bloodstream, thereby optimizing individual dosage regiments
• TDM begins when the drug is first prescribed, and involves determining an initial dosage regimen appropriate for the clinical condition and such patient characteristics as age, weight, organ function, and concomitant drug therapy
• The goal of TDM is to use appropriate concentrations of difficult-to-manage medications to optimize clinical outcomes in patients in various clinical situations
Why do we use TDM?
• Avoid toxicity
• Optimise dosage regimen for individual
• Detect changes in pharmacokinetics - interactions with other drugs
• Monitor compliance
• Response in patients depends on pharmacokinetic and pharmacodynamics variability, we can adjust to cater for pharmacokinetic variability

Sources of Variability
• Variation in absorption
• Variation in drug distribution
• Differences in an individual’s ability to metabolise and eliminate drug (e.g. genetics)
• Disease states (e.g. renal or hepatic insufficiency) or physiological states (e.g. extremes of age or obesity) that alter absorption, distribution or elimination.
• Drug interactions
• Age – whether the person has developed tolerance/susceptibility over time
• Compliance – whether they consistently take the drug
• Physiology – size, build, metabolic rate etc
Candidates for Therapeutic Drug Monitoring
• A drug is a good candidate for therapeutic drug monitoring if it exhibits the following characteristics:
- Good correlation between plasma drug concentration and pharmacological effect
- Therapeutic range determined and narrow therapeutic index
- Large inter-individual variation in pharmacokinetics (between patients)
- Toxic effects are dramatic (easily measureable)
- Desired therapeutic effect is difficult to monitor
Limitations of Therapeutic Drug Monitoring
• No well-defined therapeutic range
• Pharmacologically active metabolites and these not measured
• Toxic effects may occur unexpectedly at low concentrations as well as high concentrations
• No significant consequences associated with high or low levels
Example – Phenytoin
• Originally prescribed 300mg daily – monitoring found there to be a 10 fold variation amongst patients
Advantages
• Large inter-individual variation in pharmacokinetics
• Pharmacological effect not easily quantified
• Therapeutic range well established
• Non-linear pharmacokinetics

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