The effect of betle (Piper betle L.) leaf juice pretreatment on the pharmacokinetics of propranolol on male white rat

Agung Endro Nugroho, Arief Rahman Hakim


Drug interaction phenomenon, between drugs on drug and ford (fruit, vegetables on others), can happen in drug therapy of a disease due to the existence of compounds other than the drug (fruits, vegetables or drink). This interaction can alter and affect the action and effect of the drug. The aim of the research is to study an interaction between betle leaf (a vegetable ) and propranolol, which is a beta-blocker with a high hepatic extraction ratio, in male white rat. The study was conducted by employing a completely randomized design in male wistar inbreed rat (aged 2-2.5 months, 150-250 g). The animals in group I were given propranolol with an oral single dose of 7.5 mg/kg BW (control group) and in group II were given pretreatment with betle leaf juice dose of 17 mL/kg BW at an hour prior propranolol administration. After collected at some certain times, the drug concentration on bloods were analyzed with a Spectropflurometer.

The results shown that pretreatment of betle leaf juice did not affect the absorption rate constant (Ka) significantly (P>0.05), and increase the total clearence (ClT) and volume of distribution in steady state (Vdss) significantly (P<0.05). The increasing of both ClT and Vdss caused alteration of the secondary pharmacokinetics parameters of propranolol and these derivates significantly

(P<0.05) except the mean residence time value (MRT). This it is concluded that the pretreatment of betle leaf juice with the dose of 17 mL/kg BW affect the pharmacokinetics of propranolol or decrease the propranolol concentration in blood.

Key words : propranolol, betle leaf, pharmacokinetics and drug interaction

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Carleton, P.F., 1992, Fisiologi Sistem Kardiovaskuler, Dalam Price, S.A., dan Wilson, L.M., Fisiologi : Proses-Proses Penyakit, diterjemahkan oleh Peter Anugrah, 4th Ed., Mosby, London.

Chaudhary, D. and Kale, R.K., 2002, Antioxidant and non-toxic properties of Piper betle leaf extract : in vitro and in vivo studies, Phytother. Res., 16(5) : 461-466.

Chen, S.J., Wu, B.N., Yeh, J.L., Lo, Y.C., Chen. I.C. and Chen I.J., 1995, C-fiber-evoked autonomic cardiovasculer effects after injection of Piper betle inflorescence extracts, J. Ethnopharmacol., 45(3) : 183-188.

Curry, S.H., 1980, Drug Disposition and Pharmacokinetics with A Consideration of Pharmacological and Clinical Relationship, 3rd Ed., 225-240, Blacwell Scientific Publications, Oxford.

Darwis, 1992, Potensi sirih (Piper betle L.) sebagai tanaman obat, Warta Tumbuhan Obat Indonesia,1(1): 9.

Dollery, S.C., 1999, Propranolol, Therapeuctic Drugs, 2nd Ed., Vol. 2, Churchill Living stone, Edinburgh.

Gibaldi, M., 1984, Biopharmaceutics and Clinical Pharmacokinetics, 3rd Ed., 257-285, Lea and Febiger, Philadelphia.

Gibson, G.G. and Skett, P., 1986, Introduction to Drug Metabolism, 1-42, Chapman and Hall, London.

Hakim, L., 2001, Farmakokinetika Interaksi Obat dengan Bahan Obat Alam : Tinjauan pada Aspek Eliminasi Obat, Pidato Pengukuhan Jabatan Guru Besar pada Fakultas Farmasi UGM, Universitas Gadjah Mada, Yogyakarta.

Hardman, J.G., Limbird, L.E., Molinoff, P.B. and Ruddon, R.W.R. (Ed.), Goodman and Gilman’s The Pharmacological Basic of Therapeutics, 8th Ed., 1776, McGraw-Hill International Editions, Singapore.

Hernani dan Yuliani, S., 1992, Peranan sirih sebagai obat tradisional, Warta Tumbuhan Obat Indonesia, 1(1) : 12.

Hussar, D.A.,1995, Drug Interactions, Remington : The Science and Practice of Pharmacy, Vol. II, 19th Ed., 1822-1836, Mack Publising Company Easton, Pennsylvania.

Johnston, A and Woolland, R.C., 1483, STRIPE : A. Computer Program for Pharmacokinetics, J.Pharmacol. Meth, a : 193 – 200.

Notari. R.E.. 1980. Biopharmaceutics and Clinical Pharmacokinetics. 3rd Edition. Marcel Dekker Inc. New York.

Nurhayati, H., 1997, Pengaruh praperlakuan piperin, air perasan kencur dan kunyit terhadap

farmakokinetika propranolol pada kelinci, Skripsi, Fakultas Farmasi Universitas Gadjah Mada,


Prayogo, B. dan Sutaryadi, 1992, Pemanfaatan daun sirih untuk pelayanan kesehatan primer, Warta Tumbuhan Obat Indonesia, 1(1) : 9.

Quinn, D.I and Day, R.O, 1987, Guide to Clinically More Importannt Drug Interactions, In Speight, T.M. (Ed.), Avery’s Drug Treatment : Principles and Practice of Clinical Pharmacology and Therapeutics, 3rd Ed., 1665-1668, ADIS Press, Aucland.

Rowland, M. and Tozer., T.M., 1989, Clinical Pharmacokinetics : Concept and Application, 2nd Ed., 9-65, 246-266, Lea and Febiger, Philadelphia.

Ramji, N., Ramji, N., Iyer, R. and Chandrasekaran, S., 2002, Phenolic antibacterials from Piper betle in the prevention of halitosis, J. Ethnopharmacol., 81(1-2) : 149-152.

Ross, E.M., 1991, Pharmacodynamics : Mechanism of Drug Action and Relationship Between Drug

Concentration Effect, In Hardman, J.G., Limbird, L.E., Molinoff, P.B. and Ruddon, R.W.R.

(Ed.), Goodman and Gilman’s The Pharmacological Basic of Therapeutics, 8th Ed., 33-48, McGraw-Hill

International Editions, Singapore.

Shargel, L. and Yu., A.B.C., 1993, Applied Biopharmaceutics and Pharmacocinetics, 3 rd Ed, 318, Appleton

and Lange, Norwalk, New York.

Shitut, S., Pandit, V. and Mehta, B.K., 1999, The antimicrobial efficiency of Piper betle Linn leaf (stalk)

againts human pathogenic bacteria and phytopathogenic fungi, Cent. Eur. J. Public Health, 7(3) :


Sofia, V., 2001, Farmakokinetika propranolol pada tikus putih jantan : Pengaruh dosis dan saat

pemberian kurkuminoid, Tesis, Fakultas Farmasi Universitas Gadjah Mada, Yogyakarta.

Winarni, 1998, Pengaruh praperlakuan air perasan daun sirih terhadap farmakokinetika salisilamida dan

salisilat pada kelinci, Skripsi, Fakultas Farmasi Universitas Gadjah Mada, Yogyakarta.



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