An Amperometric Cytochrome P450-2D6 Biosensor System for the Detection of the Selective Serotonin Reuptake Inhibitors (SSRIs) Paroxetine and Fluvoxamine

Abstract:

Paroxetine is the second most prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant drug, characterized by extensive inter-individual variation in steady state plasma concentrations resulting in drug toxicity amongst patinets. A nanopolymeric biosensor for studying the biotransformation of paroxetine is presented. The bioelectrode system consists of cytochrome P450-2D6 enzyme encapsulated in nanotubular poly (8-anilino-1-napthalene sulphonic acid) electrochemically deposited on gold. The biosensing procedure involved the determination of the extent of modulation of fluvoxamine responses to the P450-2D6 enzyme electrode after incubation in paroxetine standard solutions. Paroxetine inhibited the activity of cytochrome P450-2D6 (CYP2D6) resulting in a decrease in the fluvoxamine signal of the biosensor. The biosensor gave a linear analytical response for the paroxetine in the interval 0.005 and 0.05 μM, with a detection limit of 0.002 μM and a response time of 30 s. Electrochemical Michaelis–Menten kinetics of the reversible competitive inhibition of the fluvoxamine responses of the biosensor by 0, 0.05 and 0.1 μM paroxetine gave apparent Michaelis–Menten constant (K_M^app) values of 1.00 μM, 1.11 μM and 1.25 μM, respectively. The corresponding value for the maximum response, I_MAX was 0.02 A. The dissociation constant, K_I, value evaluated from Dixon analysis of the paroxetine modulation data was estimated to be-0.02 μM while Cornish-Bowden analysis confirmed the competitive inhibitory characteristics of the enzyme.

• Periodical: Journal of Nano Research (Volume 44)
• Pages: 208-228
• DOI: https://doi.org/10.4028/www.scientific.net/JNanoR.44.208
• Online since: November 2016
• Authors: Rachel Fanelwa Ajayi*, Ezo Nxusani, Samantha F. Douman, Anovuyo Jonnas, Priscilla Gloria Lorraine Baker, Emmanuel Iheanyichukwu Iwuoha
• Keywords: Cytochrome P450-2D6, Fluvoxamine, Paroxetine, Poly(8-Anilino-1-Napthalene Sulphonic Acid), Reversible Competitive Inhibition

References

[1] M. Cristina Castelli, S. Bhaskar, J. Lippman, Pharmacokinetic Properties of Once-Daily Oral Low-Dose Mesylate Salt of Paroxetine (LDMP 7. 5 mg) Following Single and Multiple Doses in Healthy Postmenopausal Women, Clinical Therapeutics. 35 (2013).

DOI: 10.1016/j.clinthera.2013.05.001

[2] A. V. Ravindran, C. Cameron, R,. Bhatla, L. N. Ravindran, T. L. da Silva, Paroxetine in the treatment of dysthymic disorder without co-morbidities: A double-blind, placebo-controlled, flexible-dose study, Asian Journal of Psychiatry. 6 (2013).

DOI: 10.1016/j.ajp.2012.10.004

[3] M. T. Yakubu, R. O. Jimoh, Aqueous extract of Carpolobia lutea root ameliorates paroxetine-induced anti-androgenic activity in male rats, Middle East Fertility Society Journal. 20 (2015) 192-197.

DOI: 10.1016/j.mefs.2014.10.001

[4] S. Jiang, W. Zhao, Y. Chen, Z. Zhong, X. Liu, Paroxetine decreased plasma exposure of glyburide partly via inhibiting intestinal absorption in rats, Drug Metabolism and Pharmacokinetics. 30 (2015) 240-246.

DOI: 10.1016/j.dmpk.2015.02.004

[5] C. Webhofer, P. Gormanns, S. Reckow, W. Zieglgänsberger, C. W. Turck, Proteomic and metabolomic profiling reveals time-dependent changes in hippocampal metabolism upon paroxetine treatment and biomarker candidates, Journal of Psychiatric Research. 47 (2013).

DOI: 10.1016/j.jpsychires.2012.11.003

[6] A. Talati, S. P. Pantazatos, J. Hirsch, F. Schneier, A pilot study of gray matter volume changes associated with paroxetine treatment and response in social anxiety disorder, Psychiatry Research: Neuroimaging. 231, (2015) 279-285.

DOI: 10.1016/j.pscychresns.2015.01.008

[7] J. E. Agbokponto, Z. Luo, R. Liu, Z. Liu, M. Liang, L. Ding, Study of pharmacokinetic interaction of paroxetine and roxithromycin on bencycloquidium bromide in healthy subjects, European Journal of Pharmaceutical Sciences. 69 (2015) 37-43.

DOI: 10.1016/j.ejps.2014.12.019

[8] M. A. El-Nabarawi, E. R. Bendas, R. T. A. El Rehem, M. Y.S. Abary, Transdermal drug delivery of paroxetine through lipid-vesicular formulation to augment its bioavailability, International Journal of Pharmaceutics. 443 (2013) 307-317.

DOI: 10.1016/j.ijpharm.2013.01.016

[9] A. Serretti, S. Gibiino, A. Drago, Specificity profile of paroxetine in major depressive disorder: Meta-regression of double-blind, randomized clinical trials, Journal of Affective Disorders. 132 (2011) 14-25.

DOI: 10.1016/j.jad.2010.08.018

[10] R. J.T. Mocking, H. F. Verburg, A. M. Westerink, M. W.J. Koeter, H. G. Ruhé, A. H. Schene, Fatty acid metabolism and its longitudinal relationship with the hypothalamic–pituitary–adrenal axis in major depression: Associations with prospective antidepressant response, Psychoneuroendocrinology. 59 (2015).

DOI: 10.1016/j.psyneuen.2015.04.027

[11] R. Viviani, B. Abler, A. Seeringer, J. C. Stingl, Effect of paroxetine and bupropion on human resting brain perfusion: An arterial spin labeling study, NeuroImage. 61 (2012) 773-779.

DOI: 10.1016/j.neuroimage.2012.03.014

[12] N. Fani, A. Ashraf, N. Afzal, F. Jawed, N. Kitayama, L. Reed, J. D. Bremner, Increased neural response to trauma scripts in posttraumatic stress disorder following paroxetine treatment: A pilot study, Neuroscience Letters. 491 (2011) 196-201.

DOI: 10.1016/j.neulet.2011.01.037

[13] A. Serretti, S. Gibiino, A. Drago, Specificity profile of paroxetine in major depressive disorder: Meta-regression of double-blind, randomized clinical trials, Journal of Affective Disorders. 132 (2011) 14-25.

DOI: 10.1016/j.jad.2010.08.018

[14] R.J.T. Mocking, H.F. Verburg, A.M. Westerink, J. Assies, F.M. Vaz, M.W.J. Koeter, H.G. Ruhé, A.H. Schene, P. 2. b. 031 Longitudinal interplay between paroxetine response, cortisol and fatty acid metabolism in major depressive disorder, European Neuropsychopharmacology. 24 (2014).

DOI: 10.1016/s0924-977x(14)70632-7

[15] K.K. Lemberg, T.E. Heiskanen, M. Neuvonen, V.K. Kontinen, P.J. Neuvonen, M. -L. Dahl, E.A. Kalso, Does co-administration of paroxetine change oxycodone analgesia: An interaction study in chronic pain patients, Scandinavian Journal of Pain 1 (2010).

DOI: 10.1016/j.sjpain.2009.09.003

[16] M.E. Glover, P.C. Pugh, N.L. Jackson, J.L. Cohen, A.D. Fant, H. Akil, S.M. Clinton, Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats, Neuroscience. 284 (2015) 775-797.

DOI: 10.1016/j.neuroscience.2014.10.044

[17] E. Kang, H. Shim, K. Kim, J. Park, I. Lee, B. Yu, Platelet serotonin transporter function after short-term paroxetine treatment in patients with panic disorder, Psychiatry Research. 176 (2010) 250-253.

DOI: 10.1016/j.psychres.2008.12.007

[18] S. Guzzetti, E. Calcagno, A. Canetta, S. Caccia, L. Cervo, R. W. Invernizzi, Strain differences in paroxetine-induced reduction of immobility time in the forced swimming test in mice: Role of serotonin, European Journal of Pharmacology. 594 (2008).

DOI: 10.1016/j.ejphar.2008.07.031

[19] U. Freo, A. Merico, M. Ermani, C. Ori, Cerebral metabolic effects of fluoxetine, fluvoxamine, paroxetine and sertraline in the conscious rat, Neuroscience Letters. 436 (2008) 148-152.

DOI: 10.1016/j.neulet.2008.03.009

[20] E. Tudela, C. Villier, M. Mallaret, Toxic epidermal necrolysis associated with paroxetine General Hospital Psychiatry. 31 (2009) 297-298.

DOI: 10.1016/j.genhosppsych.2008.07.006

[21] I. Skelin, F. Yamane, M. Diksic, Flesinoxan challenge suggests that chronic treatment with paroxetine in rats does not desensitize receptors controlling 5-HT synthesis. Neurochemistry International. 53 (2008) 236-243.

DOI: 10.1016/j.neuint.2008.04.005

[22] J. Jiang, T. Kuhara, R. Ueki, Y. Zheng, H. Suto, S. Ikeda, H. Ogawa, Inhibitory effects of Paroxetine on the development of atopic dermatitis-like lesions in NC/Nga mice, Journal of Dermatological Science. 47 (2007) 244-247.

DOI: 10.1016/j.jdermsci.2007.05.006

[23] C. Chou, S. He, C. Jan, Paroxetine-induced apoptosis in human osteosarcoma cells: Activation of p.38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation, Applied Pharmacology. 218 (2007) 265-273.

DOI: 10.1016/j.taap.2006.11.012

[24] M. Ueda, G. Hirokane, S. Morita, K. Akiyama, K. Shimoda, The impact of CYP2D6 genotypes on the plasma concentration of paroxetine in Japanese psychiatric patients, Progress in Neuro-Psychopharmacology and Biological Psychiatry. 30 (2006) 486-491.

DOI: 10.1016/j.pnpbp.2005.11.007

[25] H. Tanii, K. Ichihashi, K. Inoue, K. Fujita, Y. Okazaki, Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam, Progress in Neuro-Psychopharmacology and Biological Psychiatry. 30 (2006) 1176-1178.

DOI: 10.1016/j.pnpbp.2006.04.006

[26] H. Juan, Z. Zhiling, L. Huande, Simultaneous determination of fluoxetine, citalopram, paroxetine, venlafaxine in plasma by high performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–MS/ESI), Journal of Chromatography B. 820 (2005).

DOI: 10.1016/j.jchromb.2005.03.006

[27] I. A. Zainaghi, V. L. Lanchote, R. H.C. Queiroz, Determination of paroxetine in geriatric depression by high-performance liquid chromatography, Pharmacological Research. 48 (2003) 217-221.

DOI: 10.1016/s1043-6618(03)00098-7

[28] B. R. Lawford, E. P. Noble, B. Kann, L. Arnold, J. Rowell, T. L. Ritchie, D2 dopamine receptor gene polymorphism: paroxetine and social functioning in posttraumatic stress disorder, European Neuropsychopharmacology. 13 (2003) 313-320.

DOI: 10.1016/s0924-977x(02)00152-9

[29] V. Knott, C. Mahoney, S. Kennedy, K. Evans, EEG correlates of acute and chronic paroxetine treatment in depression, Journal of Affective Disorders 69 (2002) 241-249.

DOI: 10.1016/s0165-0327(01)00308-1

[30] P. Du, S. Liu, P. Wu, C. Cai, Preparation and characterization of room temperature ionic liquid/single-walled carbon nanotube nanocomposites and their application to the direct electrochemistry of heme-containing proteins/enzymes, Electrochimica Acta. 52 (2007).

DOI: 10.1016/j.electacta.2007.04.092

[31] J. Owino, O. Arotiba, N. Hendricks, T. Waryo, R. Ngece, P. Baker and E. Iwuoha, Electrochemical immunosensor based on Polythionine/gold nanoparticles for the determination of Aflatoxin B1, Sensors. 8 (2008) 8262 – 8274.

DOI: 10.3390/s8128262

[32] C. Yu, X. Zhou, H. Gu, Immobilization, direct electrochemistry and electrocatalysis of hemoglobin on colloidal silver nanoparticles-chitosan film, Electrochimica Acta. 55 (2010) 8738-8743.

DOI: 10.1016/j.electacta.2010.08.010

[33] R. Mažeikiene, G. Niaura, A. Malinauskas, Raman spectroelectrochemical study of self-doped copolymers of aniline and selected aminonaphthalenesulfonates, Electrochimica Acta. 51 (2006) 1917-(1924).

DOI: 10.1016/j.electacta.2005.06.025

[34] R. Mažeikienė, G. Niaura, A. Malinauskas, In situ Raman spectroelectrochemical study of electrocatalytic oxidation of ascorbate at polyaniline- and sulfonated polyaniline-modified electrodes, Electrochimica Acta. 51 (2006) 5761-5766.

DOI: 10.1016/j.electacta.2006.03.011

[35] M. Kanungo, A. Kumar, A.Q. Contractor, Studies on electropolymerization of aniline in the presence of sodium dodecyl sulfate and its application in sensing urea, Journal of Electroanalytical Chemistry. 528, (2002) 46-56.

DOI: 10.1016/s0022-0728(02)00770-2

[36] S. Mu, C. Chen, J. Wang, The kinetic behavior for the electrochemical polymerization of aniline in aqueous solution, Synthetic Metals. 88 (1997) 249-254.

DOI: 10.1016/s0379-6779(97)03863-0

[37] N. Bistolas, U. Wollenberger, C. Jung, F.W. Scheller, Cytochrome P450 biosensors—a review, Biosensors and Bioelectronics. 20 (2005) 2408-2423.

DOI: 10.1016/j.bios.2004.11.023

[38] A. Ignaszak, N. Hendricks, R. Ngece, A. Al-Ahmed, P. Baker, E. Iwuoha, Novel therapeutic biosensor for Indinavir – A Protease Inhibitor Antiretroviral drug, Journal of Pharmeceutical and Biomedical Analysis. 49 (2009) 498 – 501.

DOI: 10.1016/j.jpba.2008.10.025

[39] L. Lin, P. Qiu, X. Cao, L. Jin, Colloidal silver nanoparticles modified electrode and its application to the electroanalysis of Cytochrome c, Electrochimica Acta. 53 (2008) 5368-5372.

DOI: 10.1016/j.electacta.2008.02.080

[40] S. Zong, Y. Cao, H. Ju, Direct Electron Transfer of Hemoglobin Immobilized in Multiwalled Carbon Nanotubes Enhanced Grafted Collagen Matrix for Electrocatalytic Detection of Hydrogen Peroxide, Electroanalysis. 19 (2007) 841– 846.

DOI: 10.1002/elan.200603783

[41] Z. Dai, Y. Xiao, X. Yu, Z. Mai, X. Zhao, Direct electrochemistry of myoglobin based on ionic liquid–clay composite films, Biosensors and Bioelectronics. 24 (2009) 1629-1634.

DOI: 10.1016/j.bios.2008.08.032

[42] U. Sidwaba, R. F. Ajayi, U. Feleni, S. Douman, R. Tshikhudo, E. I. Iwuoha, Polyanilino-Carbon Nanotubes derivatised cytochrome P450 2E1 Nanobiosensor for the determination of pyrazinamide Anti-tuberculosis drugs, Nano Hybrids. 6(2014) 59-73.

DOI: 10.4028/www.scientific.net/nh.6.59

[43] O. Tovide, N. Jahed, , R. F. Ajayi, H. R. Makelane, K. M. Molapo, E. I. Iwuoha, Electro-oxidation of anthracene on polyanilino-graphene composite electrode, Sensors and Actuators B: Chemical. 205 (2014) 184-192.

DOI: 10.1016/j.snb.2014.07.116

[44] R. F. Ajayi, U. Sidwaba, S. F. Douman, E. Nxusani, L. Wilson, C. Rassie, O. Tovide, E. I. Iwuoha, A Nanosensor System Based On Disuccinimydyl–CYP2E1 for Amperometric Detection of the Anti-Tuberculosis Drug, Pyrazinamide, World Academy of Science, Engineering and Technology International Journal of Medical, Health, Pharmaceutical and Biomedical Engineering. 8(2014).

[45] E. Laviron, The use of linear potential sweep voltammetry and of a. c. voltammetry for the study of the surface electrochemical reaction of strongly adsorbed systems and of redox modified electrodes, Journal of Electroanalytical Chemistry. 100 (1979).

DOI: 10.1016/s0022-0728(79)80167-9

[46] E. Laviron, General expression of the linear potential sweep voltammogram in the case of diffusionless electrochemical systems, J. Electroanal. Chem. 101 (1979) 19-28.

DOI: 10.1016/s0022-0728(79)80075-3

[47] R. F. Ajayi, U. Sidwaba, U. Feleni, S. F. Douman, X. G. Fuku, S. Hamid, T. T. Waryo, E. I. Iwuoha, Chemically amplified cytochrome P450-2E1 drug metabolism nanobiosensor for rifampicin anti-tuberculosis drug, Electrochimica Acta. 128 (2014).

DOI: 10.1016/j.electacta.2013.12.147

[48] O. Tovide, N. Jaheed, N. Mohamed, E. Nxusani, R. F. Ajayi, N. Njomo, R. Tshikhudo, E. I. Iwuoha, Graphenated polyaniline-doped tungsten oxide nanocomposite sensor for real time determination of phenanthrene, Electrochimica Acta. 128 (2014).

DOI: 10.1016/j.electacta.2013.12.134

[49] E. I. Iwuoha, S. Joseph, Z. Zhang, M. R Smyth, U. Fuhr, P. Montellano, Drug metabolism biosensors: electrochemical reactivities of cytochrome P450cam immobilised in synthetic vesicular systems, Journal of Pharmaceutical and Biomedical Analysis. 17 (1998).

DOI: 10.1016/s0731-7085(98)00076-4

[50] R. Eisenthal, A. Cornish-Bowden, The direct linear plot. A new graphical procedure for estimating enzyme kinetic parameters, Biochemistry Journal. 139 (1974) 715–720.

DOI: 10.1042/bj1390715

[51] R.S. Costa, D. Machad, I. Rocha, E.C. Ferreira, Hybrid dynamic modeling of Escherichia coli central metabolic network combining Michaelis-Menten and approximate kinetic equations, Biosystems. 100 (2010) 150-157.

DOI: 10.1016/j.biosystems.2010.03.001

[52] S. Rezaei-Zarchi, S. Imani, A. Javid, A. Zand, M. Saadati, Z. Zagari, Direct electron transfer of hemoglobin on nickel oxide nanoparticles modified graphite electrode, African Journal of Biochemistry. 5(2011) 165-171.

[53] M.A. 1. Abbasi, V.U. Ahmad, M. Zubair, N. Fatima, U. Farooq, M.I. Choudhary, Phosphodiesterase and thymidine phosphorylase-inhibiting salirepin derivatives from Symplocos racemosa, Planta Med. 70(2004)1189-1194.

DOI: 10.1055/s-2004-835850

[54] T. Hansmann, B. Sanson, J. Stojan, M. Weik, D. Fournier, Kinetic insight into the mechanism of cholinesterasterase inhibition by aflatoxin B1 to develop biosensors, Biosensors and Bioelectronics. 24(2009) 2119-2124.

DOI: 10.1016/j.bios.2008.11.006

[55] T. S. Maurer, A. Ghosh, N. Haddish-Berhane, A. Sawant-Basak, V. Mascitti, R.P. Robinson, Pharmacodynamic Model of Sodium–Glucose Transporter 2 (SGLT2) Inhibition: Implications for Quantitative Translational Pharmacology, AAPS J. 13(2011) 576–584.

DOI: 10.1208/s12248-011-9297-2

[56] D. K. Gosser, Cyclic Voltammetry, simulations and Analysis of Reaction Mechanisms, first ed., VCH Publishers Inc. New York. (1993).

[57] I. Kovacevic, M. Pokrajac, B. Miljkovic, D. Jovanovic, M. Prostran, Comparison of liquid chromatography with fluorescence detection to liquid chromatography–mass spectrometry for the determination of fluoxetine and norfluoxetine in human plasma, Journal of Chromatography B. 830 (2006).

DOI: 10.1016/j.jchromb.2005.11.034

[58] M. Emaduddin, H. Takeuchi, Lineweaver-burk analysis for the blocking effects of mammalian dopamine receptor antagonists on dopamine-induced currents in Achatina giant neurons, General Pharmacology: The Vascular System. 27(1996) 1209-1213.

DOI: 10.1016/s0306-3623(96)00045-6