PMID- 16542203
OWN - NLM
STAT- MEDLINE
DCOM- 20060911
LR  - 20181201
IS  - 0306-5251 (Print)
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 61
IP  - 4
DP  - 2006 Apr
TI  - Pharmacokinetics and tolerability of lamotrigine and olanzapine coadministered to 
      healthy subjects.
PG  - 420-6
AB  - AIM: To assess the pharmacokinetic effect and tolerability of lamotrigine 200 mg 
      day(-1) and olanzapine 15 mg day(-1) coadministration in healthy male volunteers. 
      METHODS: Subjects were randomized to receive either lamotrigine titrated on days 
      1-42 with olanzapine added on days 43-56 (LTG + OLZ group; N = 16), lamotrigine 
      titration with placebo added on days 43-56 (LTG group; N = 12), or placebo on 
      days 1-42 with olanzapine added on days 43-56 (OLZ group; N = 16). Steady state 
      (0-24 h) pharmacokinetic profiles were determined on day 56 in each group. 
      RESULTS: The average (90% confidence interval) ratios of lamotrigine area under 
      the concentration-time curve from 0 to 24 h and maximum observed concentration 
      for the comparison of LTG + OLZ:LTG were 0.76 (0.65, 0.90) and 0.80 (0.71, 0.90), 
      respectively. Olanzapine pharmacokinetics were essentially unaffected by 
      lamotrigine. The most frequently reported adverse events (AEs) during combination 
      therapy were fatigue, dizziness and mild transaminase elevations. These AEs 
      occurred at similar frequencies in the LTG + OLZ and OLZ cohorts, while being 
      less frequent or absent in the LTG group. CONCLUSIONS: Lamotrigine and olanzapine 
      coadministration in patients who may benefit from the combination was supported 
      by this study. Lamotrigine dosing schedules are recommended to remain unchanged 
      when combined with olanzapine therapy. However, the possibility exists that the 
      lamotrigine dose for some patients may need adjustment to optimize treatment when 
      olanzapine is added to or withdrawn from a regimen including lamotrigine.
FAU - Sidhu, Jagdev
AU  - Sidhu J
AD  - GlaxoSmithKline Research & Development, Harlow, UK. jssidhu008@hotmail.com
FAU - Job, Sarah
AU  - Job S
FAU - Bullman, Jonathan
AU  - Bullman J
FAU - Francis, Emma
AU  - Francis E
FAU - Abbott, Richard
AU  - Abbott R
FAU - Ascher, John
AU  - Ascher J
FAU - Theis, Jochen G W
AU  - Theis JG
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Antidepressive Agents)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Central Nervous System Agents)
RN  - 0 (Triazines)
RN  - 12794-10-4 (Benzodiazepines)
RN  - N7U69T4SZR (Olanzapine)
RN  - U3H27498KS (Lamotrigine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antidepressive Agents/adverse effects/blood/pharmacokinetics
MH  - Antipsychotic Agents/adverse effects/blood/pharmacokinetics
MH  - Area Under Curve
MH  - Benzodiazepines/adverse effects/blood/pharmacokinetics
MH  - Central Nervous System Agents/adverse effects/blood/*pharmacokinetics
MH  - Drug Administration Schedule
MH  - Drug Interactions
MH  - Humans
MH  - Lamotrigine
MH  - Male
MH  - Olanzapine
MH  - Triazines/adverse effects/blood/*pharmacokinetics
PMC - PMC1885046
EDAT- 2006/03/18 09:00
MHDA- 2006/09/12 09:00
PMCR- 2007/04/01
CRDT- 2006/03/18 09:00
PHST- 2006/03/18 09:00 [pubmed]
PHST- 2006/09/12 09:00 [medline]
PHST- 2006/03/18 09:00 [entrez]
PHST- 2007/04/01 00:00 [pmc-release]
AID - BCP2598 [pii]
AID - 10.1111/j.1365-2125.2006.02598.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2006 Apr;61(4):420-6. doi: 10.1111/j.1365-2125.2006.02598.x.