Lithium-drug interactions altering the intracellular lithium level: an in vitro study

Area of Science:

• Pharmacology
• Biochemistry
• Clinical Chemistry

Background:

• The red cell:plasma lithium ratio (LR) is a biomarker used in psychiatric research.
• Accurate measurement of LR is crucial for understanding lithium's efficacy and toxicity.
• In vitro systems are needed to reliably predict in vivo lithium distribution.

Purpose of the Study:

• To establish an in vitro system for predicting the in vivo red cell:plasma lithium ratio (LR).
• To investigate the effects of various psychotropic and other drugs on intracellular lithium levels.
• To identify potential drug interactions that may alter lithium pharmacokinetics.

Main Methods:

• Development of an in vitro incubation system using a bicarbonate-CO2 buffer.
• Incubation of red blood cells with lithium and various drug compounds.
• Measurement of intracellular and plasma lithium concentrations to determine the LR.

Main Results:

• The in vitro system accurately predicted the in vivo red cell:plasma lithium ratio (LR).
• Piperazine phenothiazines markedly elevated intracellular lithium, doubling the LR.
• Aminoalkyl phenothiazines, thioxanthenes, and some antipsychotics showed moderate increases in LR.
• Tricyclic antidepressants increased LR by 20-30%; other drug classes had no significant effect.
• Hydralazine was the only antihypertensive to affect LR; fluphenazine's effect involved sodium increase and was blocked by dipyridamole.

Conclusions:

• The developed in vitro system reliably predicts in vivo red cell:plasma lithium ratio (LR).
• Specific drug classes, notably piperazine phenothiazines, significantly alter intracellular lithium accumulation.
• These findings underscore the importance of considering drug interactions in lithium therapy and LR interpretation for affective disorders.