Metoprolol Population Pharmacokinetics in Older Chinese Patients With CKM Syndrome: Joint Effects of rs1065852 and CKM2S2-BAG Score on Clearance.

rs1065852 T/T genotype (CYP2D6) associated with reduced apparent clearance, adding to multi-organ burden as measured by the CKM2S2-BAG score.

Population pharmacokinetic model built on sparse real-world data from 42 Chinese patients aged 60 to 93 years with cardiovascular-kidney-metabolic (CKM) syndrome treated with immediate-release metoprolol tartrate. Pharmacokinetics were adequately described by a one-compartment model with first-order absorption and elimination, with candidate covariates including demographics, genetic polymorphism, laboratory variables, comorbidities, frailty phenotype, SARC-F score, age-adjusted Charlson Comorbidity Index, CKM stage and CKM2S2-BAG score. The rs1065852 T/T genotype and a high CKM2S2-BAG score (> 11) were associated with lower apparent clearance, with reductions of approximately 32% and 30% respectively, decreasing interindividual variability in clearance from 46.9% to 39.9%. Simulations identified subgroup-specific dosing regimens that kept steady-state trough concentrations within a literature-derived range.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The idea of stratifying jointly on genotype and on a clinical burden score is appealing, because that is how the polymedicated older patient actually presents: never a genotype alone. Its scope remains very limited, however: 42 patients, sparse data, an exposure rather than clinical endpoint, and above all genotyping reduced to rs1065852 when a full CYP2D6 status requires haplotype and copy number analysis — a limitation the authors acknowledge by calling for prospective validation. The proposed regimens are simulations, in no way validated dosing recommendations.

Analysis by Dr Thibaut Benquey