Summary
Losartan potassium (LOS), used in the treatment of hypertension, is metabolized primarily by cytochrome P450. This study investigates the effect of quercetin (QU), a CYP3A4 inducer, on the pharmacokinetics of LOS in rats. A rapid, sensitive high-performance thin-layer chromatography (HPTLC) method was developed and validated for the bioanalysis of losartan using olmesartan as internal standard (IS). The salting-out assisted liquid—liquid extraction (SALLE) employing acetonitrile and MgCl2 gave high recovery of LOS (>90%). HPTLC separation, achieved on silica gel 60 F254 plates employing toluene—ethyl acetate—acetone—formic acid (4:4:1:0.5 V/V) as the mobile phase, with densitometric analysis at 240 nm, gave good linearity (50–1200 ng mL-1) with high intra-day and i nter-day precision. LOS in plasma samples was stable when stored under different stability conditions. The pharmacokinetics of LOS was found to be significantly altered when co-administered with QU: C max = 809.8 ± 4.1 at 40 min (t max) to C max = 1124.8 ± 86.6 ng mL-1 at 120 min (t max). This study indicates the chances of herb—drug interaction when LOS is co-administered with QU, leading to its increased bioavailability, potentiating its side effect/toxic manifestation. As QU is abundantly present in herbs and dietary food, patients of LOS therapy need to be cautious while concurrently consuming herbal preparations containing QU. This study also demonstrates the utility of HPTLC as an effective tool for pharmacokinetics study for the estimation of herb—drug interactions.
Similar content being viewed by others
References
S. Brantley, A. Argikar, Y.S. Lin, S. Nagar, M.F. Paine, Herb—drug interactions: challenges and opportunities for improved predictions, Drug Metab. Dispos. 42 (2014) 301–317.
A. Fugh-Berman, E. Ernst, Herb—drug interactions: review and assessment of report reliability, Br. J. Clin. Pharmacol. 52 (2001) 587–595.
S. Bromfield, P. Muntner, High blood pressure: the leading global burden of disease risk factor and the need for worldwide prevention programs, Curr. Hypertens. Rep. 15 (2013) 134–136.
J. Daubney, P.L. Bonner, A.J. Hargreaves, J.M. Dickenson, Cardioprotective and cardiotoxic effects of quercetin and two of its in vivo metabolites on differentiated H9c2 cardiomyocytes, Basic Clin. Pharmacol. Toxicol. 116 (2015) 96–109.
A.A. Izzo, G. Di Carlo, F. Borrelli, E. Ernst, Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction, Int. J. Cardiol. 98 (2005) 1–14.
D.A. Sica, T.W. Gehr, S. Ghosh, Clinical pharmacokinetics of losartan, Clin. Pharmacokinet. 44 (2005) 797–814.
S. Liu, F.L. Bu, C.M. Wei, G.Y. Yuan, B.J. Wang, R.C. Guo, Pharmacokinetics of hydrochlorothiazide, losartan and E3174 after oral doses of losartan and losartan/hydrochlorothiazide in healthy Chinese male volunteers, Pharmacol. Pharm. 3 (2012) 7–14.
M.W. Lo, M.R. Goldberg, J.B. McCrea, H. Lu, C.I. Furtek, T.D. Bjornsson, Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans, Clin. Pharmacol. Ther. 58 (1995) 641–649.
R. Shanmugam, K. Gowthamarajan, D.L. Priyanka, K. Madhuri, V.V. Karri Narayanareddy, Bioanalytical method development and validation for herbal quercetin in nano formulation by RPU-FLC in rabbit plasm, J. Bioequiv. Availab. 5 (2013) 191–196.
S.N. Umathe, P.V. Dixit, K.U. Bansod, M.M. Wanjari, Quercetin pre-treatment increases the bioavailability of pioglitazone in rats: involvement of CYP3A inhibition, Biochem. Pharmacol. 75 (2008) 1670–1676.
E.R. Lee, G.H. Kang, S.G. Cho, Effect of flavonoids on human health: old subjects but new challenges, Recent Pat. Biotechnol. 1 (2007) 139–150.
K.J. Gohil, J.A. Patel, Herb–drug interactions: a review and study based on assessment of clinical case reports in literature, Indian J. Pharmacol. 39 (2007) 129–139.
M.C. Morand, C. D.O. Texier, F. Regerat, C. Remesy, Bioavailability of rutin and quercetin in rats, FEBS Lett. 409 (1997) 12–16.
H.J. Shah, M.L. Kundlik, N.K. Patel, G. Subbaiah, D.M. Patel, B.N. Suhagia, C.N. Patel, Rapid determination of losartan and losartan acid in human plasma by multiplexed LC–MS/MS, J. Sep. Sci. 20 (2009) 3388–3394.
A. Kumar, M. Debnath, J.V.L.N. Seshagiri Rao, G. Sankar, New validated stability indicating RP-HPLC bioanalytical method development and validation for simultaneous estimation of hydrochlorothiazide, ramipril and losartan in human plasma by using PDA detector, Pharm. Anal. Acta 6 (2017) 1–8.
V.K. Karra, N.R. Pilli, J.K. Inamadugu, J.V.L.N. Seshagiri Rao, Simultaneous determination of losartan, losartan acid and amlodipine in human plasma by LC–MS/MS and its application to a human pharmacokinetic study, Pharm Methods. 3 (2012) 18–25.
D. Goswami, A. Kumar, A.H. Khuroo, T. Monif, N.R. Thudi, V.K. Shrivastav, S.K. Dubey, A.K. Shingla, M. Prakash, S. Mehra, Pharmacokinetic estimation of losartan, losartan carboxylic acid and hydrochlorothiazide in human plasma by LC/MS/MS validated method, Clin. Res. Regul. Aff. 25 (2008) 235–258.
M. Del Rosario Brunetto, Y. Contreras, S. Clavijo, D. Torres, Y. Delgado, F. Ovalles, C. Ayala, M. Gallignani, J.M. Estela, V.C. Martin, Determination of losartan, telmisartan, and valsartan by direct injection of human urine into a column-switching liquid chromatographic system with fluorescence, J. Pharm. Biomed. Anal. 50 (2009) 194–199.
P.K. Yeung, A. Jamieson, G.J. Smith, D. Fice, P.T. Pollak, A validated RP-LC method for simultaneous determination of losartan potassium and amlodipine besilate in pharmaceutical preparations, Int. J. Pharm. 204 (2000)17–22.
S. Shivakumar, T. Sudhir, R. Mital, G. Devala Rao, S.V.S.G.B. Prasad, LC/MS/MS method for the simultaneous estimation of losartan potassium and irbesartan in rat plasma, Int. J. Pharm. Pharm. Sci. 1 (2009) 206–215.
S.K. Shetty, K.V. Surendranath, P. Radhakrishnanand, R.M. Borkar, P.S. Devrukhakar, J. Jogul, U.M. Tripathi, Quantitative application to a polypill by the development of stability indicating LC method for the simultaneous estimation of aspirin, atorvastatin, atenolol and losartan potassium, Am. J. Anal. Chem. 2 (2010) 59–69.
L. González, J.A. López, R.M. Alonso, R.M. Jiménez, Fast screening method for the determination of angiotensin II receptor antagonists in human plasma by high-performance liquid chromatography with fluorimetric detection, J. Chromatogr. A 949 (2002) 49–60.
D.L. Hertzog, J.F. McCafferty, X. Fang, R.J. Tyrrell, R.A. Reed, In vitro evidences for simvastatin and losartan potassium interaction and its in vivo implications, J. Pharm. Biomed. Anal. 30 (2002) 747–60.
R.A. Stearns, P.K. Chakravarty, R. Chen, S.H. Chi, Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members, Drug Metab. Dispos. 23 (1995) 207–215.
M. Selvadurai, S.N. Meyyanathan, Sensitive and accurate estimation of losartan potassium formulation by high-performance thin-layer chromatography, Pharm. Methods 2 (2011) 95–98.
A.K Kolsure, B.B. Chavan, A.R. Chabukswar, B.S. Kuchekar, Development and validation of a HPTLC method for simultaneous estimation of atorvastatin calcium and losartan potassium in combined dosage form, Asian J. Biomed. Pharm. 4 (2014) 20–24.
R. Dubey, V.K. Bhusari, S.R. Dhaneshwar, Validated HPTLC method for simultaneous estimation of losartan potassium and metolazone in bulk drug and formulation, Pharm. Lett. 3 (2015) 334–342.
K.B Bodiwala, K. Mali, P. Patel, P.B. Prajapati, B.P. Marolia, G.G. Kalyankar, Estimation of losartan potassium and ramipril in their combined dosage form by validated HPTLC method, Eurasian J. Anal. Chem. 12 (2017) 167–177.
K.E. McCarthy, Q. Wang, E.W Tsai, R.E. Gilbert, D.P. Ip, M.A. Brooks, Determination of losartan and its degradates in COZAAR® tablets by reversed-phase high-performance thin-layer chromatography, J. Pharm. Biomed. Anal. 17 (1998) 671–677.
S.V. Shah, I.S. Rathod, B. Suhagai, S.S. Savale, Simultaneous determination of losartan and hydrochlorothiazide in combined dosage forms by first-derivative spectroscopy and high-performance thin-layer chromatography, J. AOAC Int. 84 (2001) 1715–1723.
L.K. Santhana, S. Lakshmi, Simultaneous analysis of losartan potassium, amlodipine besylate, and hydrochlorothiazide in bulk and in tablets by high-performance thin-layer chromatography with UV–absorption densitometry, J. Anal. Methods Chem. 2012 (2012) 108281. Doi: 10.1155/2012/108281.
D. Tsvetkova, D. Obreshkova, Application of validated TLC–densitometric method for simultaneous identifi cation and determination of losartan potassium, telmisartan, and valsartan in tablets, J. Planar Chromatogr. 25 (2012) 326–330.
Guidance for Industry. Bioanalytical Method Validation, Centre for Drug Evaluation and Research (CDER), US Department of Health and Human Services, Food and Drug Administration, Rockville, MD, 2018.
D.A Sica, T.W. Gehr, S. Ghosh, Clinical pharmacokinetics of losartan, Clin. Pharmacokinet. 44 (2005) 797–814.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jadhao, S., Thomas, A., Raje, A. et al. Herb—Drug Interaction of Quercetin on the Pharmacokinetics of Losartan in Rats: A High-Performance Thin-L ayer Chromatography Study. JPC-J Planar Chromat 32, 401–409 (2019). https://doi.org/10.1556/1006.2019.32.5.8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1556/1006.2019.32.5.8