PHARMACOKINETIC INTERACTIONS BETWEEN LITHIUM AND FLUOXETINE AFTER SINGLE AND REPEATED FLUOXETINE ADMINISTRATION IN YOUNG HEALTHY-VOLUNTEERS

Pharmacokinetic interactions following coadministration of fluoxetine and lithium were investigated in 10 young healthy subjects. Both drugs were administered orally in a non-blinded design with 3 consecutive t reatment periods: single oral dose of Lithium (32.4 mmol lithium as ac etate, Quilonum; coadministration of single oral doses of lithium (32. 4 mmol) and fluoxetine (Fluctin, 60 mg); and single oral dose of lithi um after 7-day pretreatment with fluoxetine (20 mg t.i.d.). Periods 1 and 2 were separated by a 1-week washout phase, while period 3 followe d on immediately after period 2. Lithium serum concentrations were pra ctically identical in periods 1 and 3 (administration of lithium alone and after chronic fluoxetine dosing). However, in period 2, when the 2 drugs were coadministered as single oral doses, the lithium concentr ations were lower in the first 4 hours after medication compared with treatment periods 1 and 3. C-max was also significantly lower in perio d 2. The times to peak, however, were not significantly changed by any fluoxetine comedication. The parameters AUC(0-infinity), t(1/2), tota l clearance (Cl-tot) and renal clearance (Cl-ren) determined after adm inistration of Lithium alone did not differ statistically from values determined after single or after repeated fluoxetine dosing. Coadminis tration of lithium and fluoxetine did not produce any clinically relev ant changes in hemodynamics, ECGs or laboratory parameters. After sing le doses of both drugs the most frequently reported symptoms were gast rointestinal complaints, while mild sedative symptoms were predominant when lithium was given after repeated fluoxetine medication. In concl usion, the findings of this study indicate that the reported occurrenc e of neurotoxic symptoms after lithium augmentation of unsuccessful tr eatment with fluoxetine is not due to a pharmacokinetic interaction re sulting in modified lithium kinetics.