Pharmacokinetics of linalool and linalyl acetate in rats after repeated oral administration of silexan, an essential oil from Lavandula angustifolia flowers

Silexan is the active ingredient in Lasea® – an approved drug for the treatment of restlessness and mild anxiety in Germany. The naturally occurring enantiomers R-(-)linalool (L) and R-(-)-linalyl acetate (LA) are the main constituents of silexan representing 70 – 80% of the total oil. In previous studies we have reported on the pharmacokinetics of L and LA in rats after single oral administration of silexan or the two major individual constituents (Nöldner et al., 2011). We now investigated the pharmacokinetics of L and LA after repeated application of silexan (100 mg/kg/day p.o.) over a period of 14 consecutive days. The plasma and organ concentrations of L and LA were measured by headspace GC-MS for 48h after the last administration.

	Linalool				Linalyl acetate
	Single dose		Repeated doses		Single dose		Repeated doses
Tissue	Cmax (ng/ml or g)	Tmax (h)	Cmax (ng/ml or g)	Tmax (h)	Cmax (ng/ml or g)	Tmax (h)	Cmax (ng/ml or g)	Tmax (h)
Plasma	77	0.25	108	0.25	n.d.	-	n.d.	-
Brain	164	0.25	140	0.25	31	0.25	48	0.25
Liver	2287	0.25	2095	0.25	n.d.	-	25	32
Kidney	670	0.25	1547	0.25	n.d.	-	12	4
Fat	2085	4	3958	4	n.d.	-	117	2
n.d.: not detectable

The results show that both single and multiple doses of silexan result in similar concentrations of L in plasma and all analyzed organs. However, the concentrations and distribution of LA were significantly different. After single administration LA was only measured in the brain while it was detected in all tissues except the plasma after repeated administration although at low concentrations. The lower LA levels are obviously due to a very quick metabolization of LA into L. In conclusion, the results demonstrate that oral administration of silexan rapidly results in high plasma and tissue levels of L without a clear tendency for accumulation after repeated application.

References:

[1] M. Nöldner, S. Germer, E. Koch (2011). Planta Med. 77, 1410.