Pharmacokinetic interactions between lithium and fluoxetine after single and repeated fluoxetine administration in young healthy volunteers
Breuel, H.P.; Müller-Oerlinghausen, B.; Nickelsen, T.; Heine, P.R.
International Journal of Clinical Pharmacology and Therapeutics 33(7): 415-419
1995
ISSN/ISBN: 0946-1965 PMID: 7582400 Document Number: 442318
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 treatment periods: single oral dose of lithium (32.4 mmol lithium as acetate), Quilonum; coadministration of single oral doses of lithium (32.4 mmol) and fluoxetine (Fluctin, 60 mg); and single oral dose of lithium 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 followed on immediately after period 2. Lithium serum concentrations were practically 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 concentrations were lower in the first 4 hours after medication compared with treatment periods 1 and 3. C-max was also significantly lower in period 2. The times to peak, however, were not significantly changed by any fluoxetine comedication. The parameters AUC-0 fwdarw - infin , t-1/2, total clearance (Cl-tot) and renal clearance (Cl-ren) determined after administration of lithium alone did not differ statistically from values determined after single or after repeated fluoxetine dosing. Coadministration of lithium and fluoxetine did not produce any clinically relevant changes in hemodynamics, ECGs or laboratory parameters. After single doses of both drugs the most frequently reported symptoms were gastrointestinal complaints, while mild sedative symptoms were predominant when lithium was given after repeated fluoxetine medication. In conclusion. the findings of this study indicate that the reported occurrence of neurotoxic symptoms after lithium augmentation of unsuccessful treatment with fluoxetine is not due to a pharmacokinetic interaction resulting in modified lithium kinetics.