Precision Dental Pharmacotherapy: Role of Pharmacogenomics and the Oral Microbiome in Personalized Drug Therapy

Abstract

Dental pharmacotherapy is largely based on population-level evidence, although patients differ in analgesic response, adverse effects, drug exposure and susceptibility to treatment failure. Pharmacogenomics provides a biologically plausible and, for selected drug–gene pairs, clinically useful method for addressing part of this variability. CYP2D6 is particularly relevant to codeine and tramadol because genetic differences alter formation of active metabolites and can contribute to inadequate analgesia or toxicity. CYP2C9 variants can modify the pharmacokinetics of several non-steroidal anti-inflammatory drugs, although routine genotype-guided prescribing in dentistry has not yet been established. OPRM1, COMT, SCN9A and SCN10A have been investigated in relation to opioid response, pain perception and local anaesthetic efficacy, but their clinical utility remains limited. The oral microbiome represents another potential determinant of treatment response through microbial metabolism, nitrate reduction, biofilm ecology and interactions with host inflammation. However, direct evidence that oral microbial profiles can guide selection or dosing of dental medicines remains insufficient. This mini-review summarizes the most clinically relevant pharmacogenomic evidence, examines the emerging contribution of the oral microbiome, and discusses their potential application to analgesics, local anaesthetics and antimicrobial therapy. Particular emphasis is placed on evidence strength and the distinction between established pharmacogenomic guidance and exploratory biomarkers. Precision dental pharmacotherapy is most appropriately viewed as selective, evidence-based prescribing supported by validated biomarkers rather than routine broad genetic or microbiome testing.