| pA2 online © Copyright 2004 The British Pharmacological Society |
127P
University of Bath Summer Meeting July 2004 |
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Pharmacokinetics of paeoniflorin is influenced by co-administration of sinomenine in unrestrained conscious rats Zhong-Qiu Liu1, Hua Zhou1, Liang Liu1, Zhi-Hong Jiang1, Yuen-Fan Wong1, Xiong Cai1, Hong-Xi Xu2 and Kelvin Chan1. 1School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, 2Hong Kong Jockey Club Institute of Chinese Medicine Limited, Hong Kong |
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Print abstractPaeoniflorin, a characteristic monoterpene glucoside present in the root of Paeonia lactiflora Pall., is an effective immunosuppressant in treating rheumatoid arthritis. However, the clinical use of paeoniflorin has been greatly impeded by its poor bioavailability owing to the bacterial transformation in gastrointestinal tract (Takeda etal, 1997). Sinomenine, deriving from the stem of Sinomenium acutum, is another widely used antiarthritic agent ( Liu et al, 1996) .
The aim of this study is to investigate the influences of co-administrated sinomenine hydrochloride on the pharmacokinetics of paeoniflorin in rats to identify the possible interactions between paeoniflorin and sinomenine.
A single dose of paeoniflorin (150mg/kg) alone or with sinomenine hydrochloride (90mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n=5, 250~300g). Blood samples (0.2ml/time point) were collected via a jugular vein catheter before dosing and from 10min to 12 hours post-dosing. A high-performance liquid-chromatographic assay calibrated with pentoxifylline as the internal standard was employed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic parameters and profiles were derived and constructed by using the software PK Solutions 2.0 (www.summitpk.com). The pharmacokinetic parameters were compared with unpaired Student t-test (P<0.05). All procedures involving animals and their care were approved by the Committee on the Use of Human & Animal Subjects in Teaching and Research of Hong Kong Baptist University.
In comparison with paeoniflorin given alone, the concomitant administration with sinomenine elevated the peak plasma concentration of paeoniflorin from 1.3 ± 0.2 to 6.0 ± 2.5µg/ml, delayed the peak time from 45.0 ± 5.0 to 77.3 ± 17.5min, increased the AUC0-t from 116.7 ± 37.5 to 1528.3 ± 555.1µg-min/mL, prolonged the MRT (mean residence time) from 133.1 ± 38.6 to 224.1 ± 26.6 min. decreased the CL from 1.3 ± 0.4 to 0.1 ± 0.05L/min/kg, and reduced the Vd from 102.0 ± 46.0 to 16.1 ± 1.7L/min/kg. The results showed that sinomenine hydrochloride at 90mg/kg could elevate the plasma concentration, delay the peak time and consequently increase the bioavailability of paeoniflorin in rats. Mechanism of these changes is under investigation.
Liu, L. et al. (1996) Int. J. Immunopharmacol. 18, 529-543
Takeda, S. et al. (1997) J. Pharm. Pharmacol . 49, 35-39