Correlation Analysis of Blood Lithium Metabolism Kinetics and Concentration-to-Dose Ratio in Patients With...

Lithium carbonate has a narrow therapeutic window for the treatment of manic episodes and is mainly excreted via the kidneys. Hypertension may impair lithium clearance, although evidence from relevant studies is insufficient. Based on previous research on the association between hypertension and the lithium concentration-to-dose (C/D) ratio, this study further performed a large-sample stratified analysis to evaluate the independent effects of hypertension on steady-state lithium pharmacokinetics, C/D ratio, rate of achieving therapeutic lithium levels, and risk of lithium toxicity in patients with mania.

A single-center retrospective cohort study was performed, enrolling 210 patients with mania, who were assigned to a hypertension group (n = 90) or a non-hypertension group (n = 120). The t-test, chi-square test, and multiple linear regression were used to evaluate the relevant parameters.

There was no significant difference in the mean daily dose of lithium carbonate between the two groups. However, the hypertension group had significantly higher steady-state serum lithium concentrations and C/D ratios than the non-hypertension group (p < 0.001). The rate of achieving therapeutic lithium levels in the hypertension group was only 42.22%, markedly lower than the 65.83% in the non-hypertension group, while the incidence of lithium toxicity was 11.11% in the hypertension group, significantly higher than the 2.50% in the control group. Multiple regression analysis confirmed that hypertension (β = 0.215), age, and daily dose were independent influencing factors for the C/D ratio, with elderly hypertensive patients showing a more pronounced increase in the C/D ratio. The type of antihypertensive medication did not affect lithium metabolism.

Hypertension can reduce renal lithium excretion and elevate both the C/D ratio and the risk of toxicity; therefore, in clinical practice, the initial lithium dose should be reduced and therapeutic drug monitoring should be intensified for patients with comorbid hypertension, while elderly patients should receive stratified management with lower serum concentration ranges.