Track: Discovery and Basic Research - Pharmacology - Pharmacokinetics
Category: Late Breaking Poster Abstract
The Relationship between Hydrophobicity and Fraction of Drug Metabolism
Purpose: It is well-established that metabolism of drugs increases their polarity through biotransformation, which facilitates urinary excretion by limiting reabsorption in the nephron. We hypothesized that hydrophobicity of drug would be associated with a higher fraction of drug metabolized with respect to excretion unchanged in the kidney. While there is some support for this notion in the pharmacological literature, surprisingly the few primary research studies investigating this hypothesis study a very limited set of drugs or the relationship is not fully characterized. The purpose of this study is to characterize the relationship of hydrophobicity with proportion of the drug eliminated by metabolism in a large number of clinically useful drugs. Methods: Approximately 420 of the most clinically relevant drugs were studied, pooling drugs characterized as clinically useful by Goodman & Gilman’s The Pharmacologic Basis of Therapeutics (11th and 13th Ed) and from a list of the Top 300 most prescribed drugs from 2017. Log(P) was used as an index for hydrophobicity, and was obtained from Pubchem and Micromedex databases. Fraction metabolized was calculated from available datasets of percent urinary excretion (of unchanged parent drug). Since there are two major routes of elimination for drugs, fraction metabolized was approximated as (100 - % urinary excretion). Data on % urinary excretion was obtained from Goodman & Gilman’s Pharmacological Basis of Therapeutics or Pubchem. Results: There was a trend showing correlation of hydrophobicity with percent fraction metabolized, particularly for drugs whose log (P) was greater than zero. However, this was significant variability. Conclusion: There is a trend showing that the proportion of drug eliminated by metabolism correlates with hydrophobicity dataset of clinically useful drugs. However, there is significant variability deviating from this trend, particularly in very hydrophilic drugs.