Pharmacokinetic interaction between multiple-dose venlafaxine and single-dose lithium.
Venlafaxine is a structurally novel antidepressant. Because lithium and antidepressants may be administered concomitantly, it is important to determine whether the disposition of venlafaxine and lithium is affected by coadministration. An open-label study was conducted to evaluate the effects of multiple-dose, steady-state venlafaxine administration on the pharmacokinetics of a single oral dose of lithium. Analogously, the effects of administration of a single-dose of lithium on the disposition of venlafaxine and its active metabolite, O-desmethylvenlafaxine, after multiple-dose administration of venlafaxine were assessed. Administration of 600 mg lithium carbonate did not affect venlafaxine absorption. Lithium significantly reduced the renal clearance of venlafaxine from 0.053 to 0.027 L/h/kg. However, renal excretion is not a major elimination pathway for venlafaxine; thus, lithium did not affect the total clearance of venlafaxine. Lithium administration had similar effects on elimination of O-desmethylvenlafaxine. Multiple-dose administration of 50 mg of venlafaxine every 8 hours produced a slight increase in the rate of lithium absorption, but did not affect the extent of lithium absorption. Total clearance (0.026 L/h/kg) and steady-state volume of distribution (0.71 L/kg) of lithium were not affected by administration of venlafaxine. Thus, there were no clinically significant pharmacokinetic interactions between venlafaxine and lithium.
Troy
S M
SM
Clinical Research and Development, Wyeth-Ayerst Research, Philadelphia, Pennsylvania 19101-1245, USA.
Parker
V D
VD
Hicks
D R
DR
Boudino
F D
FD
Chiang
S T
ST
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003511:Cyclohexanols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000069468:Desvenlafaxine Succinate; D004334:Drug Administration Schedule; D004347:Drug Interactions; D006801:Humans; D008094:Lithium / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate; D008094:Lithium; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride