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Pharmacokinetics and tolerability of lamotrigine and olanzapine coadministered to healthy subjects
Author(s) -
Sidhu Jagdev,
Job Sarah,
Bullman Jonathan,
Francis Emma,
Abbott Richard,
Ascher John,
Theis Jochen G. W.
Publication year - 2006
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2006.02598.x
Subject(s) - lamotrigine , olanzapine , pharmacokinetics , tolerability , pharmacology , medicine , dosing , placebo , cmax , adverse effect , anesthesia , epilepsy , schizophrenia (object oriented programming) , psychiatry , alternative medicine , pathology
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that the lamotrigine dose for some patients may need adjustment to optimize treatment when olanzapine is added to or withdrawn from a regimen including lamotrigine.