Pharmacokinetic interaction between irbesartan and Orthosiphon stamineus extract in rat plasma

, Adul Munim,Rianto Setiaudy

aPharmacy Department,Faculty of Medicine and Health Sciences,Syarif Hidayatullah State Islamic University, Jakarta,Indonesia

bFaculty of Pharmacy,University of Indonesia,Jakarta,Indonesia

cFaculty of Medicine,University of Indonesia,Jakarta,Indonesia

Pharmacokinetic interaction between irbesartan and Orthosiphon stamineus extract in rat plasma

Nur Meilisa,b,*,Yahdiana Harahapb,Fadlina Chany Saputrib, Abdul Munimb,Rianto Setiabudyc

aPharmacy Department,Faculty of Medicine and Health Sciences,Syarif Hidayatullah State Islamic University, Jakarta,Indonesia

bFaculty of Pharmacy,University of Indonesia,Jakarta,Indonesia

cFaculty of Medicine,University of Indonesia,Jakarta,Indonesia

A R T I C L E I N F O

Article history:

Available online 24 November 2015

Orthosiphon stamineus

Irbesartan

Pharmacokinetics interaction

Herbs–drug interaction

Orthosiphonstamineus commonly known as kumis kucing has been used traditionally for rheumatoid,gout,renal calculus, hypertension,diabetes,etc.[1].It is often used in combination with synthetic hypertensive drugs like irbesartan.However, both effectiveness combination herbal medicine with modern pharmaceuticals,and the possible adverse effects from herb–drug interactions remain to be verifed.

This study investigated effect of O.stamineus extract to pharmacokinetics of irbesartan co-administration in Sprague Dawley rats.After O.stamineus extract pretreatment(500 mg/kg BW) for 6 days orally,on the seventh day rats were administered irbesartan(40 mg/kg BW)orally,then the blood sample were collected into heparinized tube via sinus orbitalis at 0,0.5,1, 1.5,2,2.5,3,4,8,12,24 and 36 hours after drug administration,then centrifuged at 10,000 rpm for 10 minutes to separate out plasma.The rat plasma was extracted by protein precipitation with acetonitril and analyzed by liquid chromatography tandem mass spectrometry,with an electrospray ionization(ESI) source at positive ion mode in the multiple reaction monitoring(MRM),was detected at m/z 429.1>205.9(for irbesartan), m/z 373>342.9(for sinensetin)and m/z 423.05>404.9(for losartan as internal standard).The plasma concentration irbesartan in the group combination of irbesartan and extract of O.stamineus was 4843.25 ng/mL and half time was 32.07 hours,higher and prolonged than the group irbesartan alone (2426.20 ng/mL and 23.82 hours).The pharmacokinetic profles are in Fig.1.According to the in vitro study it was shown that the extract of O.stamineus has potent inhibitory activity against CYP2C9[2],so the herb–drug interaction mechanism may be due to the inhibitor of CYP2C9,because irbesartan is also metabolized by CYP2C9.The results showed that concomitant use of irbesartan and extract of Orthosiphon stamineus increased the plasma level(Cmax)and prolonged the half life (t1/2)of irbesartan.

Fig.1–The pharmacokinetic profle of irbesartan alone (n=5)and irbesartan+extract of O.stamineus(n=5).

R E F E R E N C E S

[1]Ameer OZ,Salman IM,Asmawi MZ,et al.Orthosiphon stamineus:traditional uses,phytochemistry,pharmacology, and toxicology.J Med Food 2012;15(8):678–690.

[2]Hanapi NA,Azizi J,Ismail S,et al.Evaluation of selected Malaysian medicinal plants on phase I drug metabolizing enzymes CYP2C9,CYP2D6,and CYP3A4 activities in vitro.Int J Pharmacol 2010;1–6.

*E-mail address:nurmeilis.uin@gmail.com.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.055

1818-0876/©2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).