Interindividual Variation in Transdermal and Oral Drug Deliveries

It is generally assumed that the topical absorption of drugs is subject to more interindividual variation than the oral absorption of drugs. To date, we are unaware of any clinical studies or meta-analyses that compare the interindividual variation of transdermal and oral drug deliveries for a large number of medications. In this research article, the absorption data for 10 medications that can be used as an oral medication or a transdermal patch were compiled, and from the collected data, the interindividual variance was calculated for topical and oral absorption as an overall average and by drug. This research article also briefly reviews the pharmacokinetics and pharmacodynamics of transdermal and oral drug absorption. Our results indicate that there is considerable interindividual variation in topical and oral absorption for the 10 medications investigated. Yet, surprisingly, the calculated overall mean and median coefficient of variation (CV) for topical and oral absorption were comparable (within 10% of each other). Therefore, the interindividual variation in topical and oral absorption may not be as divergent as assumed previously. In a drug-by-drug comparison, certain medications demonstrated considerably more variation when absorbed orally versus topically and vice versa. It is unclear why certain drugs had less variation in absorption when delivered topically versus orally (or vice versa). However, patterns in drug molecular weight (MW) or octanol partition coefficient (log KOCT) could not totally explain these findings. In our analysis, the previously reported correlation between MW or log KOCT and interindividual variation in absorption could only be replicated when plotting the topical absorption CV and MW. What became clear from our analysis is that the drug itself is an important variable when considering which route of delivery (oral or topical) will provide the least amount of interindividual variation. Our study had many limitations because of study design, which may have affected our calculations and conclusions. Further experimentation is needed to support and reveal the basic science of skin or drug chemistry that can further explain these findings.