Population pharmacokinetic-based dose adjustment of tiapride in patients with impaired renal function.

BACKGROUND

Tiapride is widely used for the treatment of confusion in the elderly and for other indications. Kidney impairment is common in the elderly population and may influence tiapride pharmacokinetics. However, pharmacokinetic alterations of tiapride in patients with kidney disease have not been described so far.

METHODS

We studied tiapride pharmacokinetics in 71 predominantly elderly patients with various degrees of kidney impairment, including patients receiving hemodialysis. A population pharmacokinetic model and Monte Carlo simulations were used to evaluate tiapride exposure and optimize dosing across different degrees of renal impairment.

RESULTS

Tiapride pharmacokinetics was strongly dependent on renal function, while other tested covariates had no significant effect. Drug exposure was approximately fivefold higher in patients with severe kidney impairment, indicating the need for substantial dose reduction to prevent overdose. The model enabled development of dosing recommendations for patients with CKD, including those receiving hemodialysis. Due to prolonged elimination in advanced CKD, drug effects may persist for several days after discontinuation.

CONCLUSION

Renal function is the key determinant of tiapride pharmacokinetics. These findings provide practical dosing recommendations for elderly patients with kidney impairment and may improve the safety of tiapride therapy in clinical practice.