Stereoselective Pharmacokinetics and Chiral Inversions of Some Chiral Hydroxy Group Drugs

Fuxin       Chen; Qiaoxiu       Bai; Qingfeng       Wang; Suying       Chen; Xiaoxian       Ma; Changlong       Cai; Danni       Wang; Ahsan       Waqas; Pin       Gong

Abstract

Background: Chiral safety, especially chiral drug inversion in vivo, is the top priority of current scientific research. Medicine researchers and pharmacists often ignore that one enantiomer will be converted or partially converted to another enantiomer when it is ingested in vivo. So that, in the context that more than 50% of the listed drugs are chiral drugs, it is necessary and important to pay attention to the inversion of chiral drugs.

Methods: The metabolic and stereoselective pharmacokinetic characteristics of seven chiral drugs with one chiral center in the hydroxy group were reviewed in vivo and in vitro including the possible chiral inversion of each drug enantiomer. These seven drugs include (S)-Mandelic acid, RS-8359, Tramadol, Venlafaxine, Carvedilol, Fluoxetine and Metoprolol.

Results: The differences in stereoselective pharmacokinetics could be found for all the seven chiral drugs, since R and S isomers often exhibit different PK and PD properties. However, not every drug has shown the properties of one direction or two direction chiral inversion. For chiral hydroxyl group drugs, the redox enzyme system may be one of the key factors for chiral inversion in vivo.

Conclusion: In vitro and in vivo chiral inversion is a very complex problem and may occur during every process of ADME. Nowadays, research on chiral metabolism in the liver has the most attention, while neglecting the chiral transformation of other processes. Our review may provide the basis for the drug R&D and the safety of drugs in clinical therapy.

Keywords: Chiral drugs, chiral safety, metabolism, stereoselective pharmacokinetics, chiral inversion, drug enantiomer.

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Graphical Abstract

[1] 
Agrawal, Y.K.; Bhatt, H.G.; Raval, H.G.; Oza, P.M.; Gogoi, P.J. Chirality-a new era of therapeutics. Mini Rev. Med. Chem.,  2007, 7(5), 451-460.
[http://dx.doi.org/10.2174/138955707780619617 ] [PMID:  17504180] 
[2] 
Rapposelli, S. Effect of stereochemistry in medicinal chemistry and drug discovery. Curr. Top. Med. Chem.,  2011, 11(7), 758-759.
[http://dx.doi.org/10.2174/156802611795165179 ] [PMID:  21291401] 
[3] 
Cao, X.; Wang, W.; Wang, S.; Bao, L. Asymmetric synthesis of novel triazole derivatives and their in vitro antiviral activity and mechanism of action. Eur. J. Med. Chem.,  2017, 139, 718-725.
[http://dx.doi.org/10.1016/j.ejmech.2017.08.057 ] [PMID:  28858766] 
[4] 
Calcaterra, A.; D’Acquarica, I. The market of chiral drugs: Chiral switches versus de novo enantiomerically pure compounds. J. Pharm. Biomed. Anal.,  2018, 147, 323-340.
[http://dx.doi.org/10.1016/j.jpba.2017.07.008 ] [PMID:  28942107] 
[5] 
Kaur, U.; Shubhra, C.S.; Singh, R.; Gambhir, I.S. Deep venous thrombosis associated with thalidomide use in a case of steroid dependent erythema Nodosum leprosum-a management conundrum. Curr. Drug Saf.,  2017, 12, 140-144.
[http://dx.doi.org/10.2174/1574886312666170518153225] 
[6] 
Crippen, G.M. Chirality descriptors in QSAR. Curr. Computeraided Drug Des.,  2008, 4, 259-264.
[http://dx.doi.org/10.2174/157340908786786001] 
[7] 
Mc Coy, M. Business concentrates: Johnson Matthey buys biocatalysis company. Chem. Eng. News,  2010, 88, 20.
[8] 
Ishihara, K.; Kato, C.; Yamaguchi, H. Stereoselective reduction of carbonyl compounds with actinomycete: purification and characterization of three steroid dependent erythema Nodosum leprosum-a management. Biosci. Biotechnol. Biochem.,  2008, 72, 3249-3257.
[9] 
Yamaguchi, H.; Nakajima, N.; Ishihara, K. Purification and characterization of two nyl compounds with actinomycete: Purification and characterization of three. Biosci. Biotechnol. Biochem.,  2002, 66, 588-597.
[http://dx.doi.org/10.1271/bbb.66.588 ] [PMID:  12005054] 
[10] 
Somasundaram, S.; Hayllar, H.; Rafi, S.; Wrigglesworth, J.M.; Macpherson, A.J.; Bjarnason, I. The biochemical basis of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract: a review and a hypothesis. Scand. J. Gastroenterol.,  1995, 30(4), 289-299.
[http://dx.doi.org/10.3109/00365529509093280 ] [PMID:  7610343] 
[11] 
Wechter, W.J.; Mccracken, J.D.; Bigornia, A.E. On the mechanism of enhancement of the GI toxicity of S - flurbiprofen by its enantiomer. J. Clin. Pharmacol.,  1996, 36, 489.
[12] 
Brooks, W.H.; Guida, W.C.; Daniel, K.G. The significance of chirality in drug design and development. Curr. Top. Med. Chem.,  2011, 11(7), 760-770.
[http://dx.doi.org/10.2174/156802611795165098 ] [PMID:  21291399] 
[13] 
Zeng, S. Chiral drugs and drug safety. Pharmacy Today.,  2009, 19(10), 8-10.
[14] 
Wsól, V.; Skálová, L.; Szotáková, B. Chiral inversion of drugs: Coincidence or principle? Curr. Drug Metab.,  2004, 5(6), 517-533.
[http://dx.doi.org/10.2174/1389200043335360 ] [PMID:  15578945] 
[15] 
Shen, Q.; Wang, L.; Zhou, H.; Jiang, H.D.; Yu, L.S.; Zeng, S. Stereoselective binding of chiral drugs to plasma proteins. Acta Pharmacol. Sin.,  2013, 34(8), 998-1006.
[http://dx.doi.org/10.1038/aps.2013.78 ] [PMID:  23852086] 
[16] 
Maddi, S.; Scriba, G.; Yamsani, M.R. Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins. Drug Metabol. Drug Interact.,  2011, 26(2), 81-86.
[http://dx.doi.org/10.1515/dmdi.2011.004 ] [PMID:  21732706] 
[17] 
Tulashie, S.K.; Lorenz, H.; Seidelmorgenstern, A. Solubility of mandelic acid enantiomers and their mixtures in three chiral solvents. J. Chem. Eng. Data,  2010, 55, 5196.
[http://dx.doi.org/10.1021/je1006955] 
[18] 
Paci, E.; Pigini, D.; Caporossi, L.; De Rosa, M.; Santoro, A.; Sisto, R.; Papaleo, B.; Tranfo, G. Matrix effect in the quantitative determination of mandelic and phenylglyoxylic acid in urine samples by HPLC-MS/MS with isotopic dilution. Curr. Anal. Chem.,  2013, 9, 439-446.
[http://dx.doi.org/10.2174/1573411011309030013] 
[19] 
Tan, Z.; Li, F.; Zhao, C.; Teng, Y.; Liu, Y. Chiral separation of mandelic acid enantiomers using an aqueous two-phase system based on a thermo-sensitive polymer and dextran. Separ. Purif. Tech.,  2017, 172, 382-387.
[http://dx.doi.org/10.1016/j.seppur.2016.08.039] 
[20] 
Drummond, L.; Caldwell, J.; Wilson, H.K. The stereoselectivity of 1,2-phenylethanediol and mandelic acid metabolism and disposition in the rat. Xenobiotica,  1990, 20(2), 159-168.
[http://dx.doi.org/10.3109/00498259009047151 ] [PMID:  2333712] 
[21] 
Wang, J.Z. Stereoselective metabolism of styrene in SD rats., 2006.
[22] 
Wenker, M.A.; Kezić, S.; Monster, A.C.; de Wolff, F.A. Stereochemical metabolism of styrene in volunteers. Int. Arch. Occup. Environ. Health,  2001, 74(5), 359-365.
[http://dx.doi.org/10.1007/PL00007953 ] [PMID:  11516070] 
[23] 
Pisoschi, A.M. Improvement of alcohol dehydrogenase and horseradish peroxidase loadings in ethanol determination by a bienzyme sensor. Lett. Org. Chem.,  2013, 10, 611-616.
[http://dx.doi.org/10.2174/15701786113109990023] 
[24] 
Chen, X.; Yang, C.; Wang, P.; Zhang, X.; Bao, B.; Li, D.; Shi, R. Stereoselective biotransformation of racemic mandelic acid using immobilized laccase and (S)-mandelate dehydrogenase. Bioresour. Bioprocess.,  2017, 4(1), 2.
[http://dx.doi.org/10.1186/s40643-016-0135-3 ] [PMID:  28133593] 
[25] 
Gao, L.B.; Wang, J.Z.; Yao, T.W.; Zeng, S. Study on the metabolic mechanism of chiral inversion of S-mandelic acid in vitro. Chirality,  2012, 24(1), 86-95.
[http://dx.doi.org/10.1002/chir.21031 ] [PMID:  22139827] 
[26] 
Sanins, S.M.; Adams, W.J.; Kaiser, D.G.; Halstead, G.W.; Hosley, J.; Barnes, H.; Baillie, T.A. Mechanistic studies on the metabolic chiral inversion of R-ibuprofen in the rat. Drug Metab. Dispos.,  1991, 19(2), 405-410.
[PMID:  1676645] 
[27] 
Pacifici, G.M. Clinical pharmacology of ibuprofen and indomethacin in preterm infants with patent ductus arteriosus. Curr. Pediatr. Rev.,  2014, 10(3), 216-237.
[http://dx.doi.org/10.2174/1573396310666140228235815 ] [PMID:  25088343] 
[28] 
San Martín, M.F.; Soraci, A.; Fogel, F.; Tapia, O.; Islas, S. Chiral inversion of (R)-(-)-fenoprofen in guinea-pigs pretreated with clofibrate. Vet. Res. Commun.,  2002, 26(4), 323-332.
[http://dx.doi.org/10.1023/A:1016046810103 ] [PMID:  12184503] 
[29] 
Ahmadi, A.; Khalili, M.; Olama, Z.; Karami, S.; Nahri-Niknafs, B. Synthesis and study of analgesic and anti-inflammatory activities of amide derivatives of ibuprofen. Mini Rev. Med. Chem.,  2017, 17(9), 799-804.
[http://dx.doi.org/10.2174/1389557516666161226155951 ] [PMID:  28029080] 
[30] 
Dhiman, P.; Malik, N.; Khatkar, A. Docking-related survey on natural-product-based new monoamine oxidase inhibitors and their therapeutic potential. Comb. Chem. High Throughput Screen.,  2017, 20(6), 474-491.
[http://dx.doi.org/10.2174/1386207320666170414102814 ] [PMID:  28413973] 
[31] 
Yokoyama, T.; Karube, T.; Iwata, N. Comparative studies of the effects of RS-8359 and safrazine on monoamine oxidase in-vitro and in-vivo in mouse brain. J. Pharm. Pharmacol.,  1989, 41(1), 32-36.
[http://dx.doi.org/10.1111/j.2042-7158.1989.tb06324.x ] [PMID:  2565961] 
[32] 
Ramsay, R.R. Monoamine oxidases: the biochemistry of the proteins as targets in medicinal chemistry and drug discovery. Curr. Top. Med. Chem.,  2012, 12(20), 2189-2209.
[http://dx.doi.org/10.2174/156802612805219978 ] [PMID:  23231396] 
[33] 
Dhiman, P.; Malik, N.; Khatkar, A.; Antioxidant, M.K. xanthine oxidase and monoamine oxidase inhibitory potential of coumarins: A review. Curr. Org. Chem.,  2017, 21, 294-304.
[http://dx.doi.org/10.2174/1385272820666161021103547] 
[34] 
Ferino, G.; Vilar, S.; Matos, M.J.; Uriarte, E.; Cadoni, E. Monoamine oxidase inhibitors: Ten years of docking studies. Curr. Top. Med. Chem.,  2012, 12(20), 2145-2162.
[http://dx.doi.org/10.2174/156802612805220048 ] [PMID:  23231393] 
[35] 
Iwata, N.; Tonohiro, T.; Kozuka, M.; Kumagae, Y.; Takasaki, W.; Tanaka, Y. A novel selective and reversible MAO-A inhibitor, RS-8359: its pharmacological properties and metabolism. Int. Acad. Biomed. Drug Res.,  1996, 11, 285.
[36] 
Kapelewski, C.H.; Vandenbergh, D.J.; Klein, L.C. Effect of the monoamine oxidase inhibition on rewarding effects of nicotine in rodents. Curr. Drug Abuse Rev.,  2011, 4(2), 110-121.
[http://dx.doi.org/10.2174/1874473711104020110 ] [PMID:  21696345] 
[37] 
Takasaki, W.; Yamamura, M.; Nozaki, A.; Nitanai, T.; Sasahara, K.; Itoh, K.; Tanaka, Y. Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug-metabolizing enzymes. Chirality,  2005, 17(3), 135-141.
[http://dx.doi.org/10.1002/chir.20124 ] [PMID:  15704197] 
[38] 
Iwata, N.; Püchler, K.; Plenker, A. Pharmacology of the new reversible inhibitor of monoamine oxidase A, RS-8359. Int. Clin. Psychopharmacol.,  1997, 12(Suppl. 5), S3-S10.
[http://dx.doi.org/10.1097/00004850-199709005-00002 ] [PMID:  9466163] 
[39] 
Marquez, B.; Van Bambeke, F. ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions. Curr. Drug Targets,  2011, 12(5), 600-620.
[http://dx.doi.org/10.2174/138945011795378504 ] [PMID:  21039335] 
[40] 
van Assema, D.M.E.; van Berckel, B.N.M. Blood-brain barrier ABC-transporter P-glycoprotein in Alzheimer’s disease: Still a suspect? Curr. Pharm. Des.,  2016, 22(38), 5808-5816.
[http://dx.doi.org/10.2174/1381612822666160804094544 ] [PMID:  27494062] 
[41] 
Shafi, T.; Jabeen, I. Grid-Independent Descriptors (GRIND) analysis and SAR guided molecular docking studies to probe selectivity profiles of inhibitors of multidrug resistance transporters ABCB1 and ABCG2. Curr. Cancer Drug Targets,  2017, 17(2), 177-190.
[http://dx.doi.org/10.2174/1568009616666160901094140 ] [PMID:  27585695] 
[42] 
Ogihara, T.; Tamai, I.; Tsuji, A. In situ and in vitro evidence for stereoselective and carrier-mediated transport of monocarboxylic acids across intestinal epithelial tissue. Biol. Pharm. Bull.,  2000, 23(7), 855-859.
[http://dx.doi.org/10.1248/bpb.23.855 ] [PMID:  10919366] 
[43] 
Takasaki, W.; Yamamura, M.; Shigehara, E.; Suzuki, Y.; Tonohiro, T.; Hara, T.; Tanaka, Y. Stereoselective pharmacokinetics of RS-8359, a selective and reversible inhibitor of A-type monoamine oxidase, in rats, mice, dogs, and monkeys. Biol. Pharm. Bull.,  1999, 22(5), 498-503.
[http://dx.doi.org/10.1248/bpb.22.498 ] [PMID:  10375171] 
[44] 
Itoh, K.; Yamamura, M.; Takasaki, W.; Sasaki, T.; Masubuchi, A.; Tanaka, Y. Species differences in enantioselective 2-oxidations of RS-8359, a selective and reversible MAO-A inhibitor, and cinchona alkaloids by aldehyde oxidase. Biopharm. Drug Dispos.,  2006, 27(3), 133-139.
[http://dx.doi.org/10.1002/bdd.494 ] [PMID:  16400710] 
[45] 
Yamamura, M.; Takasaki, W.; Shigehara, E.; Suzuki, Y.; Hara, T.; Tonohiro, T.; Tanaka, Y. Xenobio. Metabol. Dispos.,  1995, 10(Suppl. 1), 444.
[46] 
Zhang, K.; Tang, C.; Rashed, M.; Cui, D.; Tombret, F.; Botte, H.; Lepage, F.; Levy, R.H.; Baillie, T.A. Metabolic chiral inversion of stiripentol in the rat. I. Mechanistic studies. Drug Metab. Dispos.,  1994, 22(4), 544-553.
[PMID:  7956728] 
[47] 
Deb, P.; Singha, J.; Chanda, I.; Chakraborty, P. Formulation development and optimization of matrix tablet of Tramadol hydrochloride. Recent Pat. Drug Deliv. Formul.,  2017, 11(1), 19-27.
[http://dx.doi.org/10.2174/1872211310666161004160304 ] [PMID:  27712568] 
[48] 
Keller, G.A.; Etchegoyen, M.C.V.; Fernandez, N.; Olivera, N.M.; Quiroga, P.N.; Belloso, W.H.; Diez, R.A.; Di Girolamo, G. Tramadol induced QTc-interval prolongation: Prevalence, clinical factors and correlation to plasma concentrations. Curr. Drug Saf.,  2016, 11(3), 206-214.
[http://dx.doi.org/10.2174/1574886311666160225150405 ] [PMID:  26916784] 
[49] 
Minai-Tehrani, D.; Eslami, M.; Khazaei, N.; Katebian, E.; Azizi, L.; Yazdi, F.; Hosseini, A.S.; Taheri, M. Inhibition and structural changes of liver alkaline phosphatase by tramadol. Drug Metab. Lett.,  2014, 8(2), 129-134.
[http://dx.doi.org/10.2174/1872312808666140506093756 ] [PMID:  24813660] 
[50] 
Minai-Tehrani, D.; Ashrafi, I.S.; Mohammadi, M.K.; Damavandifar, Z.S.; Zonouz, E.R.; Pirshahed, T.E. Comparing inhibitory effect of Tramadol on catalase of Pseudomonas aeruginosa and mouse liver. Curr. Enzym. Inhib.,  2014, 10, 53-57.
[http://dx.doi.org/10.2174/15734080113099990002] 
[51] 
Parasrampuria, R.; Vuppugalla, R.; Elliott, K.; Mehvar, R. Route-dependent stereoselective pharmacokinetics of tramadol and its active O-demethylated metabolite in rats. Chirality,  2007, 19(3), 190-196.
[http://dx.doi.org/10.1002/chir.20360 ] [PMID:  17192836] 
[52] 
Bravo, L.; Mico, J.A.; Berrocoso, E. Discovery and development of tramadol for the treatment of pain. Expert Opin. Drug Discov.,  2017, 12(12), 1281-1291.
[http://dx.doi.org/10.1080/17460441.2017.1377697 ] [PMID:  28920461] 
[53] 
Kumar, A.; Kaundal, A.; Ashawat, M.S.; Pandit, V.; Kumar, P. Colon targeted pulsatile drug delivery system of venlafaxine hydrochloride for treatment of depression. Curr. Psychopharmacol.,  2017, 6, 59-73.
[http://dx.doi.org/10.2174/2211556006666161221113127] 
[54] 
Cherkaoui, S.; Rudaz, S.; Veuthey, J.L. Nonaqueous capillary electrophoresis-mass spectrometry for separation of venlafaxine and its phase I metabolites. Electrophoresis,  2001, 22(3), 491-496.
[http://dx.doi.org/10.1002/1522-2683(200102)22:3<491:AID-ELPS491>3.0.CO;2-4 ] [PMID:  11258760] 
[55] 
Kandhwal, K.; Dey, S.; Nazarudheen, S.; Reyar, S.; Mishra, S.; Thudi, N.R.; Khuroo, A.H.; Monif, T. Establishing bioequivalence of racemic venlafaxine formulations using stereoselective assay method: Is it necessary? Chirality,  2011, 23(10), 948-954.
[http://dx.doi.org/10.1002/chir.21021 ] [PMID:  21953854] 
[56] 
Suwała, J.; Machowska, M.; Wiela-Hojeńska, A. Venlafaxine pharmacogenetics: A comprehensive review. Pharmacogenomics,  2019, 20(11), 829-845.
[http://dx.doi.org/10.2217/pgs-2019-0031 ] [PMID:  31368838] 
[57] 
Boshra, V.; Wakeel, G.A.H.E. The potential effect of Carvedilol against osteoporosis in ovariectomized rats. Curr. Drug Ther.,  2013, 8, 164-170.
[http://dx.doi.org/10.2174/15748855113086660010] 
[58] 
Lymperopoulos, A.; McCrink, K.A.; Brill, A. Impact of CYP2D6 genetic variation on the response of the cardiovascular patient to Carvedilol and Metoprolol. Curr. Drug Metab.,  2015, 17(1), 30-36.
[http://dx.doi.org/10.2174/1389200217666151105125425 ] [PMID:  26537419] 
[59] 
Szentmiklosi, A.J.; Szentandrássy, N.; Hegyi, B.; Horvath, B.; Magyar, J.; Bányász, T.; Nanasi, P.P. Chemistry, physiology, and pharmacology of β-adrenergic mechanisms in the heart. Why are β-blocker antiarrhythmics superior? Curr. Pharm. Des.,  2015, 21(8), 1030-1041.
[http://dx.doi.org/10.2174/1381612820666141029111240 ] [PMID:  25354180] 
[60] 
Poggi, J.C.; Da Silva, F.G.; Coelho, E.B.; Marques, M.P.; Bertucci, C.; Lanchote, V.L. Analysis of carvedilol enantiomers in human plasma using chiral stationary phase column and liquid chromatography with tandem mass spectrometry. Chirality,  2012, 24(3), 209-214.
[http://dx.doi.org/10.1002/chir.21984 ] [PMID:  22271587] 
[61] 
Parker, B.M.; Rogers, S.L.; Lymperopoulos, A. Clinical pharmacogenomics of carvedilol: the stereo-selective metabolism angle. Pharmacogenomics,  2018, 19(14), 1089-1093.
[http://dx.doi.org/10.2217/pgs-2018-0115 ] [PMID:  30086658] 
[62] 
Cardoso, J.L.; Lanchote, V.L.; Pereira, M.P.; Capela, J.M.; Lepera, J.S. Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats. Chirality,  2013, 25(3), 206-210.
[http://dx.doi.org/10.1002/chir.22136 ] [PMID:  23362155] 
[63] 
Shiha, A.A.; de la Rosa, R.F.; Delgado, M.; Pozo, M.A.; García-García, L. Subacute Fluoxetine reduces signs of hippocampal damage induced by a single convulsant dose of 4-Aminopyridine in rats. CNS Neurol. Disord. Drug Targets,  2017, 16(6), 694-704.
[http://dx.doi.org/10.2174/1871527315666160720121723 ] [PMID:  27989232] 
[64] 
Peng, L.; Gu, L.; Li, B.; Hertz, L. Fluoxetine and all other SSRIs are 5-HT2B agonists - importance for their therapeutic effects. Curr. Neuropharmacol.,  2014, 12(4), 365-379.
[http://dx.doi.org/10.2174/1570159X12666140828221720 ] [PMID:  25342944] 
[65] 
Hemeryck, A.; Belpaire, F.M. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: An update. Curr. Drug Metab.,  2002, 3(1), 13-37.
[http://dx.doi.org/10.2174/1389200023338017 ] [PMID:  11876575] 
[66] 
Stuchal, L.D.; Kleinow, K.M.; Stegeman, J.J.; James, M.O. Demethylation of the pesticide methoxychlor in liver and intestine from untreated, methoxychlor-treated, and 3-methylcholanthrene-treated channel catfish (Ictalurus punctatus): Evidence for roles of CYP1 and CYP3A family isozymes. Drug Metab. Dispos.,  2006, 34(6), 932-938.
[http://dx.doi.org/10.1124/dmd.105.009068 ] [PMID:  16510540] 
[67] 
Recber, T.; Ozkan, E.; Eren-Kocak, E.Y. lmaz, M.; Nemutlu, E.; K?r, S. A simple extraction procedure for HPLC analysis of fluoxetine in rat plasma samples. Curr. Pharm. Anal.,  2017, 13, 80-84.
[http://dx.doi.org/10.2174/1573412912666160422153616] 
[68] 
Ring, B.J.; Eckstein, J.A.; Gillespie, J.S.; Binkley, S.N.; VandenBranden, M.; Wrighton, S.A. Identification of the human cytochromes p450 responsible for in vitro formation of R- and S-norfluoxetine. J. Pharmacol. Exp. Ther.,  2001, 297(3), 1044-1050.
[PMID:  11356927] 
[69] 
Lutz, J.D.; VandenBrink, B.M.; Babu, K.N.; Nelson, W.L.; Kunze, K.L.; Isoherranen, N. Stereoselective inhibition of CYP2C19 and CYP3A4 by fluoxetine and its metabolite: Implications for risk assessment of multiple time-dependent inhibitor systems. Drug Metab. Dispos.,  2013, 41(12), 2056-2065.
[http://dx.doi.org/10.1124/dmd.113.052639 ] [PMID:  23785064] 
[70] 
Liu, L.; Fu, M.; Pei, S.; Zhou, L.; Shang, J. R-Fluoxetine increases melanin synthesis through a 5-HT1A/2A receptor and p38 MAPK signaling pathways. Int. J. Mol. Sci.,  2018, 20(1), 80.
[http://dx.doi.org/10.3390/ijms20010080 ] [PMID:  30585252] 
[71] 
Nguyen, K.T.; Ita, K.B.; Parikh, S.J.; Popova, I.E.; Bair, D.A. Transdermal delivery of Captopril and Metoprolol tartrate with microneedles. Drug Deliv. Lett.,  2014, 4, 236-243.
[http://dx.doi.org/10.2174/2210303104666141001003127] 
[72] 
Mostafavi, S.A.; Foster, R.T. Pharmacokinetics of metoprolol enantiomers following single and multiple administration of racemate in rat. Int. J. Pharm.,  2000, 202(1-2), 97-102.
[http://dx.doi.org/10.1016/S0378-5173(00)00430-0 ] [PMID:  10915931] 
[73] 
Varghese, A.; Savai, J.; Mistry, S.; Khandare, P.; Barve, K.; Pandita, N.; Gaud, R. In vitro CYP2D inhibitory effect and influence on pharmacokinetics and pharmacodynamic parameters of Metoprolol succinate by Terminalia arjuna in rats. Drug Metab. Lett.,  2016, 10(2), 124-135.
[http://dx.doi.org/10.2174/1872312810666160219121415 ] [PMID:  26891872] 
[74] 
Boralli, V.B.; Coelho, E.B.; Lanchote, V.L. Influence of quinidine, cimetidine, and ketoconazole on the enantioselective pharmacokinetics and metabolism of metoprolol in rats. Chirality,  2009, 21(10), 886-893.
[http://dx.doi.org/10.1002/chir.20682 ] [PMID:  19161215] 
[75] 
Berger, B.; Bachmann, F.; Duthaler, U.; Krähenbühl, S.; Haschke, M. Cytochrome P450 enzymes involved in metoprolol metabolism and use of metoprolol as a CYP2D6 phenotyping probe drug. Front. Pharmacol.,  2018, 9, 774.
[http://dx.doi.org/10.3389/fphar.2018.00774 ] [PMID:  30087611] 

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DOI https://dx.doi.org/10.2174/1389201021666200727144053	Print ISSN 1389-2010
Publisher Name Bentham Science Publisher	Online ISSN 1873-4316

Current Pharmaceutical Biotechnology

Stereoselective Pharmacokinetics and Chiral Inversions of Some Chiral Hydroxy Group Drugs

Abstract

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Artificial Intelligence in Bioinformatics

Current Pharmaceutical Biotechnology

Stereoselective Pharmacokinetics and Chiral Inversions of Some Chiral Hydroxy Group Drugs

Abstract

Graphical Abstract

Call for Papers in Thematic Issues

Artificial Intelligence in Bioinformatics

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