Stereoselective drug disposition: potential for misinterpretation of drug disposition data.

TLDR

Chiral drugs often have enantiomer‑specific pharmacokinetics, yet many studies use non‑stereoselective assays on racemates. The study theoretically examines how non‑stereoselective assays can misinterpret drug disposition data for racemic drugs. The authors use a theoretical framework to analyze data from non‑stereoselective assays on racemic drugs. The analysis shows that non‑stereoselective assays can yield inaccurate clearance estimates and suggest false time dependence, underscoring the importance of stereoselectivity in clinical studies. References 1–4 are cited.

Abstract

1. Although it is well recognised that the enantiomers of a chiral drug may possess different pharmacokinetic and pharmacodynamic properties, many studies dealing with chiral drugs which are administered as their racemates rely on non‐stereoselective analytical techniques. 2. We present a theoretical analysis to illustrate the potential which exists for misinterpretation of drug disposition and plasma drug concentration‐ effect data generated for a racemic drug using a non‐stereoselective assay. 3. It was shown that the use of such an analytical method can lead to the collection of data which may be both quantitatively and qualitatively inaccurate with respect to the individual enantiomers. For example, the clearance of the unresolved drug may indicate concentration‐ and time‐dependence even though this pharmacokinetic process is concentration‐ and time‐independent for each of the enantiomers. 4. The problems discussed emphasise the need to consider stereoselectivity in clinical pharmacological studies involving racemic drugs.