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Issue 15, 2017, Issue in Progress
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Pharmacokinetics of rosmarinic acid in rats by LC-MS/MS: absolute bioavailability and dose proportionality

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Abstract

Rosmarinic acid (RA), one of the main bioactive compounds of Rosmarinus officinalis L., exhibits diverse pharmacological effects. However, its oral absolute bioavailability and dose proportionality in vivo have not been comprehensively studied. In the present study, a validated LC-MS/MS method was developed for the determination of RA in rat plasma. Pharmacokinetic parameters were obtained following oral and intravenous dosing using DAS 3.0 software. Absolute bioavailability in rats was determined by comparing pharmacokinetic data after administration of single oral (12.5, 25 and 50 mg kg−1) and intravenous (0.625 mg kg−1) doses of RA. The dose proportionality of AUC and Cmax were analyzed using a power model. After single-dose oral administration of RA, Cmax values for groups with 12.5, 25 and 50 mg kg−1 doses ranged from 215.29 to 790.96 ng mL−1, with AUC0–t values from 41 789.84 to 96 070.00 min ng mL−1, while Tmax and t1/2 values ranged from 8.33 to 18.33 and from 332.34 to 295.32 min, respectively. The power model showed RA lacked dose proportionality over the dose range from 12.5–50 mg kg−1. Oral absolute bioavailability was calculated to range from 0.91% to 1.69%. All the results demonstrated that the pharmacokinetic properties of RA in rats after oral administration were characterized as rapid absorption, middle-speed elimination and poor absolute bioavailability. Systemic exposure exhibited lack of dose proportionality over the dose range from 12.5 to 50 mg kg−1. These presented data could provide useful information for the rational clinical application and optimal dosage form design of RA.

Graphical abstract: Pharmacokinetics of rosmarinic acid in rats by LC-MS/MS: absolute bioavailability and dose proportionality

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Article information


Submitted
15 Dec 2016
Accepted
21 Jan 2017
First published
30 Jan 2017

This article is Open Access

RSC Adv., 2017,7, 9057-9063
Article type
Paper

Pharmacokinetics of rosmarinic acid in rats by LC-MS/MS: absolute bioavailability and dose proportionality

J. Wang, G. Li, T. Rui, A. Kang, G. Li, T. Fu, J. Li, L. Di and B. Cai, RSC Adv., 2017, 7, 9057
DOI: 10.1039/C6RA28237G

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