Objectives: To evaluate the possible pharmacokinetic interaction between nefazodone and lithium.
Methods: Twelve healthy volunteers received nefazodone 200 mg b.i.d. for 5 days. A 4-day washout phase followed from day 6 to day 9. From day 10 to day 20, escalating doses of lithium 250 mg b.i.d. to 500 mg b.i.d. were given; the daily dose of 1000 mg was obtained on day 13. From day 16 to day 20, nefazodone 200 mg b.i.d. was added to the lithium dosing regimen. Venous blood sampling was performed on days 5, 15 and 20 for 0- to 48-h-pharmacokinetic analysis. Nefazodone and its metabolites, hydroxynefazodone, mCPP and triazoledione were assayed by high-performance liquid chromatography (HPLC). Lithium was assayed by flame photometry.
Results: Co-administration of nefazodone did not modify pharmacokinetic parameters of lithium at steady-state. Comparison of the area under the plasma or serum concentration-versus-time curve calculated from 0-12 h (AUC0-12) of nefazodone and hydroxynefazodone revealed no significant differences when nefazodone was administered alone or with lithium. The mean maximum peak plasma concentration Cmax and AUC0-12 of meta-chlorophenyl-piperazine (mCPP) were significantly reduced by 27% (P < 0.001) and 16% (P < 0.001) with the co-administration. The mean Cmax and AUC0-12 of triazoledione were reduced by 23% (P < 0.005) and 16% (P < 0.01) by the co-administration.
Conclusion: Since there were no clinically significant changes in the pharmacokinetics of the parent compounds or metabolites, and the combination was well tolerated, no dosage adjustments of nefazodone or lithium are necessary when they are co-administered.
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http://dx.doi.org/10.1007/s002280050576 | DOI Listing |
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Department of Ecology, Environment and Plant Sciences, Stockholm University, Stockholm, Sweden.
Accumulating evidence is suggesting more frequent tropical-to-temperate transitions than previously thought. This raises the possibility that biome transitions could be facilitated by precursor traits. A wealth of ecological, genetic and physiological evidence suggests overlap between drought and frost stress responses, but the origin of this overlap, i.
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University of Chicago, Department of Psychiatry and Behavioral Neuroscience, Chicago, IL.
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