ISSN - 0975-7058 Special Issue (October) EFFECT OF 70% ETHANOL EXTRACT OF ORTHOSIPHONIS STAMINEUS BENTH LEAVES ON THE PHARMACOKINETIC PARAMETERS OF FUROSEMIDE IN MALE WHITE RATS RIANA MAYA OKTAVIANI, SANTI PURNA SARI*, YAHDIANA HARAHAP Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia. Email: santisari@farmasi.ui.ac.id Received: 21 April 2017, Revised and Accepted: 18 August 2017 ABSTRACT Objective: This study aimed to observe the effect of the 70% ethanol extract of Orthosiphonis stamineus Benth leaves on the pharmacokinetic parameters of furosemide in white male rats. Methods: 18 Sprague–Dawley male rats were divided into three groups: The normal control group was given only 1% carboxymethyl cellulose, the furosemide group was given 7.2 mg/200 g body weight (BW) suspension of furosemide, and the combination group was given 700 mg/kg BW suspension of the 70% ethanolic extract of O. stamineus Benth leaves for 4 days followed by a 7.2 mg/200 g BW suspension of furosemide. On the 4 th day of treatment, we performed orbital sinus blood sampling on the eyes of the rats and analyzed the levels of furosemide in plasma using high- performance liquid chromatography. Results: Therefore, the results showed that the administration of the 70% ethanol extract of O. stamineus Benth leaves improves the pharmacokinetic parameters of furosemide on Cp max and the area under the curve (p<0.05). Conclusion: This study concludes that the 70% ethanol extract of O. stamineus Benth leaves improves the pharmacokinetic parameters of furosemide in white male rats. Keywords: Cat’s whiskers leaves, Furosemide, Orthosiphonis stamineus Benth, Pharmacokinetic, 70% ethanolic extract. INTRODUCTION Furosemide is an anthranilic acid derivative drug included in powerful diuretics. Based on the research conducted by Bragatto et al. [1], a single dose of 40 mg furosemide given orally produced significant results in increasing the volume of urine and had a pharmacokinetics ratio interval of C max (93.63-121.92%), area under the curve (AUC 0−t ) (96.80-115.72%), and AUC 0−∞ (98.45-117.43%). Another study mentions that the administration of furosemide with a dose of 8 mg/200 g body weight (BW) produced AUC 0−∞ 13.52±52.29 µg/mL hr with C max 22:34±4:39 µg/mL [2]. Indonesian herbal medicine has been used for hundreds of years, long before the advent of modern medicine that involves a diagnostic laboratory and chemicals [3]. The results of basic medical research in 2010 showed that about 59.12% of Indonesia’s population consumes herbs [4]. Cat’s whiskers is a medicinal plant that has been empirically shown to act as a diuretic. Tensigard ® is a phytopharmacological preparation containing extracts of cat’s whiskers leaves combined with celery extract and is used as an antihypertensive due to its diuretic properties. The use of cat’s whiskers leaf extract and furosemide at the same time can cause a pharmacokinetic interaction that can increase or decrease furosemide levels in plasma. As a result, drug toxicity and drug effectiveness may also increase or decrease [5]. The diuretic effect of cat’s whiskers leaf extract is demonstrated by the inhibition of adenosine receptor A 1 , which will inhibit sodium reabsorption in the proximal tubules [6], and the diuretic mechanism of furosemide diuretic inhibits reabsorption of electrolytes Na + /K + /2Cl − in the ascending limb of the loop of Henle in the thick epithelium section. The diuretic effect of cat’s whiskers leaf extract and furosemide was similarly with inhibiting sodium reabsorption in the nephron [7]. The changes in the levels of the combined drugs will affect the pharmacokinetic parameters of furosemide, and this study observes the influence of cat’s whiskers leaf extract on the pharmacokinetic parameters of furosemide in white male rats using blood plasma samples. MATERIALS AND METHODS Materials The material sample used in this study was the 70% ethanol extract of cat’s whiskers leaf (Orthosiphonis stamineus Benth.) obtained from the Research Center for Spices and Medicinal Plants. Determination of cat’s whiskers leaf was conducted by the Indonesian Institute of Sciences, Bogor Botanical Gardens. Animals used in this study were 30 Sprague–Dawley rats: 12 samples for the optimization of timing and 18 for the actual test. The rats were male, approximately 3 months old and approximately 200 g in weight, and were obtained from the Institut Pertanian Bogor. The chemicals used include furosemide (Kimia Farma), furosemide standard (BPFI), propranolol HCl (BPFI), carboxymethyl cellulose (CMC) (Brataco Chemical), methanol (high- performance liquid chromatography [HPLC] grade, Merck), phosphoric acid (85%) (Merck), ethyl acetate (Merck), human blood plasma from Palang Merah Indonesia, Aqua Bidest distilled water, food standards for test animals, anhydride acetic acid, Mayer’s reagent, Dragendorff’s reagent, Bouchard’s reagent, Molisch’s reagent, iron (III) chloride reactant solution, hydrochloric acid, zinc powder, and magnesium powder. Instruments The instruments used in this study were stomach probes, syringes (Terumo), animal scales, an analytical balance (Ohaus), microhematocrit capillary tubes, a set of HPLC LC-10AD VP tools (Shimadzu) consisting of a pump, an injector, C 18 column of RP-18e (Waters, Sunfire TM 5 μm; 250 × 4.6 mm), detector SPD-20A ultraviolet-visible (UV-Vis), DGU-12A degasser, SCL-10A VP controller, and data processing on a computer, UV-1601 (Shimadzu), pH meter (Eutech pH 700), vortex (Maxi Mix II), microcentrifugator (Spectrafuge 16 M), refrigerator (Lab Tech), centrifugator (Digisystem), evaporator (Caliper), microtube, centrifuge tubes, 0.45 µm membrane filter, micropipette and pipette (blue tip/ yellow tip), reaction tube, test tube rack, vaporizer cup, beaker (Pyrex), spatula, stir bar, measuring glass (Pyrex), and flask (Pyrex). Research Article PTMDS 2017 | The 1 st Physics and Technologies in Medicine and Dentistry Symposium © 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ijap.2017.v9 s1 .28_33