Pharmacokineticspharmacodynamics in clinical oncology

Most drugs have a narrow therapeutic index—dosages required for anti-tumour efficacy usually cause some side-effects and a small increase above the therapeutic dose may be sufficient to cause life-threatening toxicity. Variations in pharmacokinetic parameters of anti-cancer drugs between patients are frequently observed. These variations are caused by diversity in renal or metabolic functions (which are themselves due to advanced disease), drug-drug interactions, and toxic effects of previous chemotherapy on organ functions. These all contribute to variations in drug concentration in patients treated with a similar dose of cytotoxic.

Since the amount of drug reaching the site of action (tumour cells or the tissue expressing toxicity such as bone marrow stem cells) is dependent on the systemic concentration, correlation between pharmacokinetic parameters (e.g. peak concentration, AUC) and pharmacodynamics endpoints is closer than that between administered dose and pharmacodynamics. The ultimate goal of pharmaco-kinetically-guided dosing will be to maximize the likelihood of producing the antitumour response with minimum normal tissue damage.

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