Patient Compliance and its Impact on Steady State Pharmacokinetics
Physicians commonly prescribe drug products in a multiple dosage regimen (e.g., one daily or q.d., twice daily or b.i.d, etc.) for prolonged therapeutic activity. The purpose of a multiple dose regimen is to maintain the drug plasma concentration within its therapeutic window (i.e., the concentration of drug in the serum or plasma should yield optimal benefit at a minimal risk of toxicity). To study the effect of multiple dosing on drug concentration in blood, researchers often employ a deterministic model with the assumptions that drugs are administered at a fixed dosage, with fixed (usually constant) dosing intervals. In practice, as is well known in the medical community, patients may not follow such a rigid schedule. Hence, two possible scenarios might occur: patients might not take the prescribed dosage, resulting in irregular dosing amounts; or they might not adhere to the dosing schedule, resulting in irregular dosing times. This chapter intends to lay out a probability framework to model these two types of noncompliance and consequently study their impact on the steady state pharmacokinetics in a rigorous setting.
KeywordsMarkov Chain Model Dose Time Steady State Pharmacokinetic Multiple Dose Regimen Trough Concentration Series
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