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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Research Article

Evaluation of Pharmacokinetic Interaction of Cilostazol with Metoclopramide after Oral Administration in Human

Author(s): Iram Kaukab, Syed Nisar Hussain Shah, Zelal Kharaba, Ghulam Murtaza*, Abubaker Ali Saad and Shakeel Ahmad

Volume 20, Issue 11, 2019

Page: [924 - 928] Pages: 5

DOI: 10.2174/1389200220666191105115805

Price: $65

Abstract

Background: Metoclopramide is mainly metabolized by CYP2D6, CYP3A4, CYP2C19, and CYP1A2 enzymes, while cilostazol is also metabolized by CYP3A4, CYP2C19, and CYP1A2 enzymes.

Aim: This study evaluates the effect of cilostazol on the pharmacokinetics of oral metoclopramide.

Methods: This was a randomized, two-phase cross-over pharmacokinetic study separated by a 4-week wash-out time period, 12 healthy non-smoking volunteers received metoclopramide 20 mg as a single oral dose and after 4 weeks, cilostazol 100 mg twice daily for 4 days then with metoclopramide 20 mg on test day. Serial blood samples were analyzed by using a validated high-performance liquid chromatography-ultraviolet method to determine maximum plasma drug concentration (Cmax), time to reach (Tmax), and area under the curve (AUC0-∞) of metoclopramide.

Results: Cilostazol increased the mean Cmax, AUC0-∞ and half-life (T1/2) of metoclopramide by 6%, 27% and by 0.79 %, respectively. In addition, Tmax of metoclopramide was delayed by cilostazol.

Conclusion: The results showed delayed Tmax of metoclopramide by cilostazol, which could lead to the conclusion that cilostazol affects the absorption of metoclopramide. Both drugs when necessary to administer together must not be administered at the same time especially when given in gastroparesis patients.

Keywords: Cilostazol, CYP substrate, interaction, metabolism, metoclopramide, pharmacokinetics.

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[1]
Kaukab, I.; Shah, S.N.H.; Murtaza, G. Single-dose pharmacokinetics of metoclopramide oral tablets utilizing HPLC-UV Method. Curr. Pharm. Anal., 2019, 15(7), 703-709.
[http://dx.doi.org/10.2174/1573412914666180425123202]
[2]
Chua, E.W.; Harger, S.P.; Kennedy, M.A. Metoclopramide-induced acute dystonic reactions may be associated with the CYP2D6 poor metabolizer status and pregnancy-related hormonal changes. Front. Pharmacol., 2019, 10, 931.
[http://dx.doi.org/10.3389/fphar.2019.00931] [PMID: 31507424]
[3]
Choo, K.H.; Manikam, R.A.L.; Yoong, K.P.Y.; Kandasamy, V.A.P. Prophylactic metoclopramide use in trauma patients given tramadol: A randomised, double-blinded, placebo-controlled trial. Hong Kong J. Emerg. Med., 2019, 26(2), 98-105.
[http://dx.doi.org/10.1177/1024907918789586]
[4]
Tonini, M.; Candura, S.M.; Messori, E.; Rizzi, C.A. Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis. Pharmacol. Res., 1995, 31(5), 257-260.
[http://dx.doi.org/10.1016/1043-6618(95)80029-8] [PMID: 7479521]
[5]
Hibbs, A.M.; Lorch, S.A. Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review. Pediatrics, 2006, 118(2), 746-752.
[http://dx.doi.org/10.1542/peds.2005-2664] [PMID: 16882832]
[6]
McCallum, R.W.; Kline, M.M.; Curry, N.; Sturdevant, R.A.L. Comparative effects of metoclopramide and bethanechol on lower esophageal sphincter pressure in reflux patients. Gastroenterology, 1975, 68(5 Pt 1), 1114-1118.
[PMID: 1092585]
[7]
Doran, A.; Obach, R.S.; Smith, B.J.; Hosea, N.A.; Becker, S.; Callegari, E.; Chen, C.; Chen, X.; Choo, E.; Cianfrogna, J.; Cox, L.M.; Gibbs, J.P.; Gibbs, M.A.; Hatch, H.; Hop, C.E.; Kasman, I.N.; Laperle, J.; Liu, J.; Liu, X.; Logman, M.; Maclin, D.; Nedza, F.M.; Nelson, F.; Olson, E.; Rahematpura, S.; Raunig, D.; Rogers, S.; Schmidt, K.; Spracklin, D.K.; Szewc, M.; Troutman, M.; Tseng, E.; Tu, M.; Van Deusen, J.W.; Venkatakrishnan, K.; Walens, G.; Wang, E.Q.; Wong, D.; Yasgar, A.S.; Zhang, C. The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model. Drug Metab. Dispos., 2005, 33(1), 165-174.
[http://dx.doi.org/10.1124/dmd.104.001230] [PMID: 15502009]
[8]
Kwon, S.U.; Cho, Y.J.; Koo, J.S.; Bae, H.J.; Lee, Y.S.; Hong, K.S.; Lee, J.H.; Kim, J.S. Cilostazol prevents the progression of the symptomatic intracranial arterial stenosis: the multicenter double-blind placebo-controlled trial of cilostazol in symptomatic intracranial arterial stenosis. Stroke, 2005, 36(4), 782-786.
[http://dx.doi.org/10.1161/01.STR.0000157667.06542.b7] [PMID: 15746463]
[9]
Desta, Z.; Wu, G.M.; Morocho, A.M.; Flockhart, D.A. The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6. Drug Metab. Dispos., 2002, 30(3), 336-343.
[http://dx.doi.org/10.1124/dmd.30.3.336] [PMID: 11854155]
[10]
Kim, J.R.; Jung, J.A.; Kim, S.; Huh, W.; Ghim, J.L.; Shin, J.G.; Ko, J.W. Effect of cilostazol on the pharmacokinetics of simvastatin in healthy subjects. BioMed Res. Int., 2019, 20191365180
[http://dx.doi.org/10.1155/2019/1365180] [PMID: 30729119]
[11]
Yu, J.; Paine, M.J.; Maréchal, J.D.; Kemp, C.A.; Ward, C.J.; Brown, S.; Sutcliffe, M.J.; Roberts, G.C.; Rankin, E.M.; Wolf, C.R. In silico prediction of drug binding to CYP2D6: Identification of a new metabolite of metoclopramide. Drug Metab. Dispos., 2006, 34(8), 1386-1392.
[http://dx.doi.org/10.1124/dmd.106.009852] [PMID: 16698891]
[12]
Livezey, M.R.; Briggs, E.D.; Bolles, A.K.; Nagy, L.D.; Fujiwara, R.; Furge, L.L. Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6. Xenobiotica, 2014, 44(4), 309-319.
[http://dx.doi.org/10.3109/00498254.2013.835885] [PMID: 24010633]
[13]
Hogle, B.C.; Guan, X.; Folan, M.M.; Xie, W. PXR as a mediator of herb-drug interaction. Yao Wu Shi Pin Fen Xi, 2018, 26(2S), S26-S31.
[http://dx.doi.org/10.1016/j.jfda.2017.11.007] [PMID: 29703383]
[14]
Craig, W.R.; Hanlon-Dearman, A.; Sinclair, C.; Taback, S.; Moffatt, M. Metoclopramide, thickened feedings, and positioning for gastro-oesophageal reflux in children under two years. Cochrane Database Sys. Rev., 2004, 4CD003502
[http://dx.doi.org/10.1002/14651858.CD003502.pub2] [PMID: 15495056]
[15]
Lim, T.H.; Cho, Y.A.; Choi, D.H. Effects of cilostazol on the pharmacokinetics of carvedilol after oral and intravenous administration in rats. J. Physiol. Pharmacol., 2015, 66(4), 591-597.
[PMID: 26348083]
[16]
Peh, K.K.; Yuen, K.H. Indirect gastrointestinal transit monitoring and absorption of theophylline. Int. J. Pharm., 1996, 139(1-2), 95-103.
[http://dx.doi.org/10.1016/0378-5173(96)04602-9]
[17]
Ravindran, S.; Suthar, J.K.; Rokade, R.; Deshpande, P.; Singh, P.; Pratinidhi, A.; Khambadkhar, R.; Utekar, S. Pharmacokinetics, metabolism, distribution and permeability of nanomedicine. Curr. Drug Metab., 2018, 19(4), 327-334.
[http://dx.doi.org/10.2174/1389200219666180305154119] [PMID: 29512450]
[18]
Sun, P.; Liu, K. Drug-drug interactions of angiotensin converting enzyme inhibitors mediated by metabolizing enzymes and transporters. Curr. Drug Metab., 2018, 19(13), 1119-1129.
[http://dx.doi.org/10.2174/1389200219666180730163953] [PMID: 30062958]
[19]
Hebbard, G.S.; Sun, W.M.; Bochner, F.; Horowitz, M. Pharmacokinetic considerations in gastrointestinal motor disorders. Clin. Pharmacokinet., 1995, 28(1), 41-66.
[http://dx.doi.org/10.2165/00003088-199528010-00005] [PMID: 7712661]
[20]
Haruta, S.; Iwasaki, N.; Ogawara, K.; Higaki, K.; Kimura, T. Absorption behavior of orally administered drugs in rats treated with propantheline. J. Pharm. Sci., 1998, 87(9), 1081-1085.
[http://dx.doi.org/10.1021/js980117+] [PMID: 9724558]
[21]
Pöyhiä, R.; Olkkola, K.T.; Seppälä, T.; Kalso, E. The pharmacokinetics of oxycodone after intravenous injection in adults. Br. J. Clin. Pharmacol., 1991, 32(4), 516-518.
[http://dx.doi.org/10.1111/j.1365-2125.1991.tb03942.x] [PMID: 1958450]
[22]
Lin, S-P.; Yu, C-P.; Hou, Y-C.; Huang, C-Y.; Ho, L-C.; Chan, S-L. Transporter-mediated interaction of indican and methotrexate in rats. Yao Wu Shi Pin Fen Xi, 2018, 26(2S), S133-S140.
[http://dx.doi.org/10.1016/j.jfda.2017.11.006] [PMID: 29703382]
[23]
Raish, M.; Ahmad, A.; Ansari, M.A.; Alkharfy, K.M.; Ahad, A.; Khan, A.; Aljenobi, F.I.; Ali, N.; Al-Mohizea, A.M. Effect of sinapic acid on aripiprazole pharmacokinetics in rats: Possible food drug interaction. Yao Wu Shi Pin Fen Xi, 2019, 27(1), 332-338.
[http://dx.doi.org/10.1016/j.jfda.2018.06.002] [PMID: 30648588]
[24]
Yu, C-P.; Huang, C-Y.; Lin, S-P.; Hou, Y-C. Activation of P-glycoprotein and CYP 3A by coptidis rhizoma in vivo: Using cyclosporine as a probe substrate in rats. Yao Wu Shi Pin Fen Xi, 2018, 26(2S), S125-S132.
[http://dx.doi.org/10.1016/j.jfda.2017.11.005] [PMID: 29703381]
[25]
Lai, R.E.; Jay, C.E.; Sweet, D.H. Organic solute carrier 22 (SLC22) family: Potential for interactions with food, herbal/dietary supplements, endogenous compounds, and drugs. Yao Wu Shi Pin Fen Xi, 2018, 26(2S), S45-S60.
[http://dx.doi.org/10.1016/j.jfda.2018.03.002] [PMID: 29703386]

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