Genetic predictors of morphine concentration: ABCB1 polymorphisms’ importance in palliative oncology

Background. Morphine pharmacokinetics in cancer patients are characterized by high interindividual variability, partly due to genetic factors. The role of ABCB1 gene polymorphisms in modifying morphine exposure in this patient population has been poorly studied.

Objective. To evaluate the effect of ABCB1 gene polymorphisms rs1128503, rs2032582, and rs1045642 on steady-state plasma morphine concentrations in patients with cancer receiving palliative care.

Methods. This study included 86 patients with cancer treated in the Palliative Care Department of the Moscow Multidisciplinary Palliative Care Center of the Moscow Department of Health. All participants received stable oral morphine doses ranging from 30 to 100 mg/day. ABCB1 polymorphisms were genotyped using real-time polymerase chain reaction (PCR). Plasma morphine concentrations were determined using HPLC-MS/MS. Statistical analysis included an assessment of normality (Shapiro-Wilk test), nonparametric Mann–Whitney and Kruskal-Wallis tests, and χ², with p ≤ 0.05 considered statistically significant.

Results. In carriers of the TT genotype rs1045642, at a dose of 80–100 mg/day, the median morphine concentration was 151.8 nmol/L, exceeding the values in CT (110.4 nmol/L) and CC (83.7 nmol/L), with p = 0.097 (χ²), p ≤ 0.05 for pairwise comparisons. Similar trends were found for rs2032582 and rs1128503,

with significant differences between carriers of minor alleles. No adverse events related to the study intervention were reported.

Conclusion. Carriage of certain ABCB1 allelic variants is associated with increased exposure to morphine. Genetic predictors may facilitate individualized dosing in patients with cancer undergoing palliative care.

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