Pharmacopsychiatry 2014; 47 - A15
DOI: 10.1055/s-0034-1386841

Pharmacokinetic interaction between valproic acid, meropenem and risperidone

M Kuzin 1, CB Eap 2, G Gründer 1, M Paulzen 1
  • 1Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA – Translational Brain Medicine
  • 2Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, University of Lausanne, Switzerland

Objective: The addition of the beta-lactam antibiotic meropenem to an ongoing therapy with valproic acid leads to a well-known decrease of serum valproic acid (VPA) concentration. Previously unknown is the influence of this pharmacokinetic interaction on a concurrent treatment with the antipsychotic risperidone. We therefore report the effects of a complex interaction between valproic acid, meropenem and risperidone. The addition of the beta-lactam antibiotic meropenem led to a decrease of serum levels of valproic acid and a concurrent increase of the risperidone serum levels.

Methods: A patient with polydrug abuse and a comorbid psychosis was treated with valproic acid and risperidone under stable psychopathology. Because of bilateral multiple phlegmons of the forearm with bone involvement due to ongoing intravenous drug abuse, meropenem was added temporarily. Therapeutic drug monitoring (TDM) was performed to control for drug levels of valproic acid and risperidone and for optimization of treatment. Genotyping of cytochrome P450 2D6, 2C9 and 2C19 was performed to complete the clinical diagnostic.

Results: After starting the antibiotic treatment, TDM revealed a dramatic decrease of valproic acid serum levels. At the same time an increase of risperidone, but not the 9-OH-risperidone drug levels could be observed. Cytochrome P450 genotyping showed a poor metabolizer (PM) status for 2D6, an extensive metabolizer (EM) status for 2C9 and a rapid metabolizer status for 2C19.

Conclusion: Here, we could show a pharmacokinetic interaction between the beta-lactam antibiotic meropenem and both concurrent administered psychotropic drugs, risperidone and VPA. The observed increase of risperidone with a concomitant meropenem treatment indicates its possible inhibitory effects on CYP2D6, which is responsible for the formation of the active metabolite 9-OH-risperidone. A reduction in serum levels of VPA of more than 50% to a sub-therapeutic level after starting the treatment with meropenem indicates most likely an influence on the glucuronidation of valproic acid, which plays a key role in the metabolism of valproic acid, and because CYP2C9 and CYP2C19 only play a minor role in the metabolism of VPA. Our case shows the usefulness of TDM even in clinically complex situations and underscores the clinical importance of measuring serum or plasma levels for treatment optimization.