Pharmacokinetic variability

Definition : “Inter-individual variations of a drugs pharmacokinetic parameters, resulting in fairly different plasma concentration-time profiles after administration of the same dose to different patients.”DescriptionSubstantial differences in response to most drugs exist among patients. Therefore, the therapeutic standard dose of a drug, which is based on trails in healthy volunteers and patients, is not suitable for every patient. Variability exists in both pharmacokinetics and pharmacodynamics.For a typical drug, one standard deviation in the values observed for bioavailability (F), clearance (CL) and volume of distribution (Vd) would be about 20%, 50% and 30% respectively. Therefore, 95% of the time, the average concentration (Cav) will be between 35% and 270% of the target value.The most important factors in variability of pharmacokinetic parameters are:GeneticDiseaseAge and body sizeConcomitant drugsEnvironmental factors (e.g. foods, pollutants)Other factors include compliance, pregnancy, alcohol intake, seasonal variations, gender, or conditions of drug intake.Clinical implicationsIndividualization of dosage regimen to a particular patient is critical for optimal therapy. This is particularly true for drugs with a narrow therapeutic window.Until recently, reasonable individual estimates of dosage regimen were based on the patient’s weight, age, renal, hepatic and cardiovascular function and concomitant drug administration. Taking into account genetic markers is now proposed to complete dosage regimen decisions.

Source: Pharmacokinetic variability

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