Pharmacokinetics of valerenic acid after single and multiple doses of valerian in older women

Abstract

Insomnia is a commonly reported clinical problem with as many as 50% of older adults reporting difficulty in falling and/or remaining asleep. Valerian (Valeriana officinalis) is a commonly used herb that has been advocated for promoting sleep. Valerenic acid is used as a marker for quantitative analysis of valerian products with evidence of pharmacological activity relevant to the hypnotic effects of valerian. The objective of this study was to determine the pharmacokinetics of valerenic acid in a group of elderly women after receiving a single nightly valerian dose and after 2 weeks of valerian dosing. There was not a statistically significant difference in the average peak concentration (C(max)), time to maximum concentration (T(max)) area under the time curve (AUC), elimination half-life (T(1/2)) and oral clearance after a single dose compared with multiple dosing. There was considerable inter- and intra-subject variability in the pharmacokinetic parameters. C(max) and AUC deceased and T(1/2) increased with increased body weight. The variability between the capsules was extremely low: 2.2%, 1.4% and 1.4%, for hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid, respectively. In conclusion, large variability in the pharmacokinetics of valerenic acid may contribute to the inconsistencies in the effect of valerian as a sleep aid.

Pharmacokinetics of Valerenic Acid in Rats after Intravenous and Oral Administrations

“…The high V z of 6-10 L • kg −1 suggested that the compound was rapidly taken up by body tissues. Compartmental analysis revealed that the apparent volume of distribution in steady state This assumption is supported by the data of Anderson et al [10] who found a considerable inter-and intra-subject variability in the PK parameters of VA where C max and AUC decreased and t 1/2 increased with increasing body weight. The authors, therefore, speculated that higher doses of valerian were needed in patients with a higher body weight.…”

“…Until now, detailed pharmacokinetic data of VA are lacking. In a recent study Anderson et al [10] determined plasma levels of valerenic acid in older women after oral administration of single and multiple doses (300 mg) of a commercial valerian root preparation standardized to 0.8 % VA. The authors found no differences in the average peak Abstract !…”

“…However, they noticed a considerable inter-and intrasubject variability in the PK parameters. The authors concluded that the high variability in plasma levels of VA could contribute to the inconsistent effects of VA on sleep [10]. For the assessment of the efficacy of valerian products, there is a need for quantitative data regarding absorption, metabolism, and other pharmacokinetic properties of VA.…”

Review of Safety and Efficacy of Sleep Medicines in Older Adults

“…216,217 Unfortunately, the FDA does not regulate their production, and the various formulations contain different amounts of valerian. 216,218 Although the exact mechanism of valerian for insomnia is unknown, it is believed to have important interactions with the neurotransmitter GABA and its receptors. Valerian is thought to inhibit the uptake of GABA and also stimulate its release.…”

Is there anything special about valerian?

“…The relatively wide variability in drug elimination half-life among individuals gives valerian an apparently low average efficacy. 46 However, outcomes for empirically treated clinical patients are probably better than those of drug trial volunteers, who are usually treated with a single dose or a limited range of doses.…”