The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Absorption, Metabolism, and Excretion of Paliperidone, a New Monoaminergic Antagonist, in Humans
Abstract
Absorption, metabolism, and excretion of paliperidone, an atypical antipsychotic, was studied in five healthy male subjects after a single dose of 1 mg of [(14)C]paliperidone oral solution ( approximately 16 microCi/subject). One week after dosing, 88.4 to 93.8% (mean 91.1%) of the administered radioactivity was excreted: 77.1 to 87.1% (mean 79.6%) in urine and 6.8 to 14.4% (mean 11.4%) in the feces. Paliperidone was the major circulating compound (97% of the area under the plasma concentration-time curve at 24 h). No metabolites could be detected in plasma. Renal excretion was the major route of elimination with 59% of the dose excreted unchanged in urine. About half of the renal excretion occurred by active secretion. Unchanged drug was not detected in feces. Four metabolic pathways were identified as being involved in the elimination of paliperidone, each of which accounted for up to a maximum of 6.5% of the biotransformation of the total dose. Biotransformation of the drug occurred through oxidative N-dealkylation (formation of the acid metabolite M1), monohydroxylation of the alicyclic ring (M9), alcohol dehydrogenation (formation of the ketone metabolite M12), and benzisoxazole scission (formation of M11), the latter in combination with glucuronidation (M16) or alicyclic hydroxylation (M10). Unchanged drug, M1, M9, M12, and M16 were detected in urine; M10 and M11 were detected in feces. The monohydroxylated metabolite M9 was solely present in urine samples of extensive CYP2D6 metabolizers, whereas M10, another metabolite monohydroxylated at the alicyclic ring system, was present in feces of poor metabolizers as well. In conclusion, paliperidone is not metabolized extensively and is primarily renally excreted.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Paliperidone is primarily renally cleared and not extensively metabolized in the liver; 59% of a single dose is excreted in the urine unchanged [43, 77].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [43]
Citations
Cites
Bioanalytical Method Validation—A Revisit with a Decade of Progress
Shah, V. P., Midha, K. K., Findlay, J. W. A., Hill, H. M., Hulse, J. D., McGilveray, I. J., McKay, G., Miller, K. J., Patnaik, R. N., Powell, M. L., et al. (2000) · Pharmaceutical Research · doi:10.1023/a:1007669411738 · Cited by 1,574
Schotte, A., Janssen, P. F. M., Gommeren, W., Luyten, W. H. M. L., Gompel, P. V., Lesage, A. S., Loore, K. D., & Leysen, J. E. (1996) · Psychopharmacology · doi:10.1007/bf02245606 · Cited by 1,167
Schmid, B., Bircher, J., Preisig, R., & Kupfer, A. (1985) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1985.235 · Cited by 383
Kane, J. M., Cañas, F., Kramer, M. L., Ford, L., Gassmann-Mayer, C., Lim, P., & Eerdekens, M. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.09.012 · Cited by 297
Self-citationAbsorption, metabolism, and excretion of risperidone in humans.
Mannens, G., Huang, M., Meuldermans, W., Hendrickx, J., Woestenborghs, R. J. H., & Heykants, J. (1993) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08211-x · Cited by 261
Self-citationDavidson, M., Emsley, R. A., Kramer, M. L., Ford, L., Pan, G., Lim, P., & Eerdekens, M. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.03.003 · Cited by 249
Self-citationMetabolism of risperidone to 9-hydroxyrisperidone by human cytochromes P450 2D6 and 3A4
Fang, J., Bourin, M., & Baker, G. B. (1999) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/pl00005334 · Cited by 237
Marder, S. R., Kramer, M. L., Ford, L., Eerdekens, E., Lim, P., Eerdekens, M., & Lowy, A. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.01.017 · Cited by 228
Self-citationKramer, M. L., Simpson, G. M., Mačiulis, V., Kushner, S. F., Vijapurkar, U., Lim, P., & Eerdekens, M. (2007) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e31802dda4a · Cited by 219
Self-citationPlasma protein binding of risperidone and its distribution in blood
Mannens, G., Meuldermans, W., Snoeck, E., & Heykants, J. (1994) · Psychopharmacology · doi:10.1007/bf02244986 · Cited by 101
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Karlsson, 2005, Pharmacokinetics and dopamine D2 and serotonin 5-HT2A receptor occupancy of paliperidone in healthy subjects (Abstract), Eur Neuropsychopharmacol, 15, S385
Cited by
Sorted by citations
Wang, J., Sánchez‐Roselló, M., Aceña, J. L., del Pozo, C., Sorochinsky, A. E., Fustero, S., Soloshonok, V. A., & Liu, H. (2013) · Chemical Reviews · doi:10.1021/cr4002879 · Cited by 4,902
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017
Hiemke, C., Bergemann, N., Clement, H. ‐., Conca, A., Deckert, J., Domschke, K., Eckermann, G., Egberts, K. M., Gerlach, M., Greiner, C., et al. (2017) · Pharmacopsychiatry · doi:10.1055/s-0043-116492 · Cited by 1,494
Correll, C. U., Kim, E., Sliwa, J. K., Hamm, W., Gopal, S., Mathews, M., Venkatasubramanian, R., & Saklad, S. R. (2021) · CNS Drugs · doi:10.1007/s40263-020-00779-5 · Cited by 205
Oral paliperidone for schizophrenia
Nussbaum, A. M., & Stroup, T. S. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006369.pub2 · Cited by 195
Meltzer, H. Y., Bobo, W. V., Nuahmah, I. F., Lane, R., Hough, D. W., Kramer, M. L., & Eerdekens, M. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0515 · Cited by 158
Self-citationThe Pharmacokinetics of Paliperidone Versus Risperidone
de León, J., Wynn, G. H., & Sandson, N. B. (2010) · Psychosomatics · doi:10.1016/s0033-3182(10)70664-2 · Cited by 121
Therapeutic Drug Monitoring of Common Antipsychotics
Patteet, L., Morrens, M., Maudens, K. E. K., Niemegeers, P., Sabbe, B., & Neels, H. M. (2012) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e3182708ec5 · Cited by 107
Schoretsanitis, G., Spina, E., Hiemke, C., & de León, J. (2017) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2017.1345623 · Cited by 94
Safety and Pharmacokinetics of Atypical Antipsychotics in Children and Adolescents
Caccia, S. (2013) · Pediatric Drugs · doi:10.1007/s40272-013-0024-6 · Cited by 94
“subjects with severe hepatic impairment [89], and in young patients with schizophrenia and schizoaffective disorder renal clearance may be less than in adults at steady state after oral doses of ER paliperidone [90].”
InfluentialA Focused Review on the Treatment of Pediatric Patients with Atypical Antipsychotics
Lee, E. S., Vidal, C., & Findling, R. L. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2018.0037 · Cited by 82
“It is eliminated primarily through renal excretion (Vermeir et al.2008).”
Gopal, S., Gassmann-Mayer, C., Palumbo, J., Samtani, M. N., Shiwach, R., & Alphs, L. D. (2009) · Current Medical Research and Opinion · doi:10.1185/03007990903482772 · Cited by 73
Darville, N., van Heerden, M., Mariën, D., Meulder, M. D., Rossenu, S., Vermeulen, A., Vynckier, A., Jonghe, S. D., Sterkens, P., Annaert, P., et al. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.03.041 · Cited by 72
Self-citationDosing and Switching Strategies for Paliperidone Palmitate
Samtani, M. N., Gopal, S., Gassmann-Mayer, C., Alphs, L. D., & Palumbo, J. (2011) · CNS Drugs · doi:10.2165/11591690-000000000-00000 · Cited by 68
Risperidone long-acting injection: a review of its long term safety and efficacy
Rainer, M. K. (2008) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s3311 · Cited by 68
“At therapeutic doses, most of the drug is excreted unchanged through the kidneys (Veirmeir et al 2008) and its minimal hepatic metabolism might offer a safety advantage over its parent drug in patients with liver impairment and those who use other prescription drugs which compete with risperidone…”
BackgroundA review of paliperidone palmitate
Chue, P. S., & Chue, J. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.137 · Cited by 66
Vandenberghe, F., Guidi, M., Choong, E., von Gunten, A., Conus, P., Csajka, C., & Eap, C. B. (2015) · Clinical Pharmacokinetics · doi:10.1007/s40262-015-0289-8 · Cited by 60
Gunes, A., Spina, E., Dahl, M., & Scordo, M. G. (2008) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e3181858ca9 · Cited by 59
“One minor metabolic pathway has been suggested to be catalyzed by CYP2D6, but its contribution to the total elimination of the compound seems minor.(39) Both risperidone and 9-hydroxyrisperidone have been shown to be substrates for P-gp-mediated efflux.”
BackgroundAnesthetic Considerations for Patients on Psychotropic Drug Therapies
Harbell, M. W., Dumitrascu, C., Bettini, L. M., Yu, S., Thiele, C. M., & Koyyalamudi, V. (2021) · Neurology International · doi:10.3390/neurolint13040062 · Cited by 60
“Cytochrome P450 CYP3A4 and CYP2D6 enzymes have been implicated in the metabolism of paliperidone [25].”
BackgroundSerum concentrations of paliperidone versus risperidone and clinical effects
Nazirizadeh, Y., Vogel, F., Bader, W., Haen, E., Pfuhlmann, B., Gründer, G., Paulzen, M., Schwarz, M., Zernig, G., & Hiemke, C. (2010) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-010-0812-7 · Cited by 51
“Since paliperidone does not undergo significant hepatic metabolism [ 6 ], it is also well tolerated by patients with poor hepatic function, and it is not susceptible to metabolic drug interactions.”
BackgroundResultInfluentialSchoretsanitis, G., Spina, E., Hiemke, C., & de Leon, J. (2018) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2018.1549489 · Cited by 50
“The effect of having a poor metabolizer (PM) phenotype was small, which is compatible with what we know of the very limited role of CYP2D6 in paliperidone metabolism [32] and the lack of effect of these CYP2D6 inhibitors on oral paliperidone TDM [39].”
BackgroundNew atypical antipsychotics for schizophrenia: iloperidone
Caccia, S. (2010) · Drug Design Development and Therapy · doi:10.2147/dddt.s6443 · Cited by 49
“33,34 Like most antipsychotics iloperidone undergoes extensive presystemic elimination and is cleared through multiple metabolic pathways mediated by different enzymes (exceptions are amisulpride and paliperidone whose clearance are largely trough urinary excretion; see for reviews 21,39 ).”
Schoretsanitis, G., Spina, E., Hiemke, C., & de León, J. (2018) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2018.1478727 · Cited by 42
“In a third study, researchers classified patients under strong CYP2D6 inhibitors as CYP2D6 poor metabolizers, but no information on the percentage of these patients was provided [41].”
BackgroundInfluentialBacterial Degradation of Risperidone and Paliperidone in Decomposing Blood
Butzbach, D. M., Stockham, P. C., Kobus, H. J., Sims, D. N., Byard, R. W., Lokan, R. J., & Walker, G. (2012) · Journal of Forensic Sciences · doi:10.1111/j.1556-4029.2012.02280.x · Cited by 41
“There are no reports of their presence in antemortem blood or urine specimens (20,21).”
BackgroundHepatic Safety of Atypical Antipsychotics: Current Evidence and Future Directions
Slim, M., Medina‐Cáliz, I., Gonzalez-Jimenez, A., Cabello, M. R., Mayoral, F., Lucena, M. I., & Andrade, R. J. (2016) · Drug Safety · doi:10.1007/s40264-016-0436-7 · Cited by 41
“Unlike risperidone, paliperidone is characterized by limited hepatic metabolism, with approximately 60 % of the drug being eliminated unchanged in the urine [124].”
Locatelli, I., Kastelic, M., Koprivšek, J., Kores-Plesničar, B., Mrhar, A., Dolžan, V., & Grabnar, I. (2010) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2010.06.016 · Cited by 41
Hart, X. M., Gründer, G., Ansermot, N., Conca, A., Corruble, E., Crettol, S., Cumming, P. D., Frajerman, A., Hefner, G., Howes, O. D., et al. (2024) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2024.2366235 · Cited by 39
Paliperidone Extended‐Release for the Treatment of Schizophrenia
Marino, J., & Caballero, J. (2008) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.28.10.1283 · Cited by 38
Boom, S., Talluri, K., Janssens, L., Remmerie, B. M. M., Meulder, M. D., Rossenu, S., Osselaer, N. V., Eerdekens, M., & Cleton, A. (2009) · The Journal of Clinical Pharmacology · doi:10.1177/0091270009339190 · Cited by 35
“The CLR of paliperidone ER is approximately 16% of the CL/F after administration, whereas it is 58% after the administration of an IR formulation of paliperidone.(17) This difference can be explained by the difference in bioavailability of the 2 formulations: 28% for paliperidone ER and approximately 100% for paliperi…”
BackgroundMethodInfluentialSelf-citationCitrome, L. (2012) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2012.693160 · Cited by 35
Álamo, C. (2013) · Clinical and Experimental Pharmacology · doi:10.4172/2161-1459.1000117 · Cited by 35
“Furthermore, in vitro studies of human, hepatic microsomes in subjects with genotypes UGT1A1 and UGT1A6 found that those enzymes do not influence paliperidone metabolism either [36,37].”
BackgroundInfluentialCanuso, C. M., Grinspan, A., Kalali, A. H., Damaraju, C. V., Merriman, U., Alphs, L. D., & Awad, A. G. (2010) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e3283372977 · Cited by 33
“Moreover, paliperidone is not extensively metabolized by the liver (minimal metabolism by CYP450 isoenzymes) (Vermeir et al., 2008), which may further minimize interindividual pharmacokinetic variability.”
BackgroundMishra, J., & Kumar, A. (2014) · Neurotoxicity Research · doi:10.1007/s12640-014-9469-9 · Cited by 31
Mahatthanatrakul, W., Sriwiriyajan, S., Ridtitid, W., Boonleang, J., Wongnawa, M., Rujimamahasan, N., & Pipatrattanaseree, W. (2011) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.2011.01271.x · Cited by 30
Which psychotropic medications induce hepatotoxicity?
Sedky, K., Nazir, R., Joshi, A., Kaur, G., & Lippmann, S. (2011) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2011.10.007 · Cited by 31
“Paliperidone may be preferred for treating psychotic patients with a compromised hepatic status [70].”
BackgroundThyssen, A., Cleton, A., Talluri, K., Leempoels, J., Janssens, L., Boom, S., & Eerdekens, M. (2009) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1049 · Cited by 29
“As paliperidone may, in part, be metabolized by CYP3A4 (Vermeir et al., 2008) and transported by P-glycoprotein (Annaert et al.”
BackgroundInfluentialSelf-citationReview of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics
Toja-Camba, F. J., Gesto-Antelo, N., Maroñas, O., Arrieta, E. E., Zarra‐Ferro, I., González‐Barcia, M., Bandín‐Vilar, E., Sanjuan, V. M., Facal, F., Arrojo, M., et al. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13070935 · Cited by 29
“[86] Oral 5 Caucasian 51 5/0 PM/NM * Irrelevant”
BackgroundSerum Concentrations of Paliperidone After Administration of the Long-Acting Injectable Formulation
Helland, A., & Spigset, O. (2017) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0000000000000457 · Cited by 27
Pani, L., & Marchese, G. (2009) · Expert Opinion on Drug Delivery · doi:10.1517/17425240902780158 · Cited by 27
“The pharmacokinetic of paliperidone was also analyzed in a small number of CYP2D6 poor (n = 2) and extensive (n = 3) metabolizers treated with paliperidone liquid solution (an IR formulation of paliperidone) and no differences could be observed between the two genetic groups in the plasma concentration of paliperidone…”
BackgroundInfluentialPaliperidone extended-release: does it have a place in antipsychotic therapy?
Gahr, Kölle, Schoenfeldt-Lecuona, C., Lepping, P., & Freudenmann, R. W. (2011) · Drug Design Development and Therapy · doi:10.2147/dddt.s17266 · Cited by 25
Paliperidone Palmitate Intramuscular 3-Monthly Formulation: A Review in Schizophrenia
Lamb, Y. N., & Keating, G. M. (2016) · Drugs · doi:10.1007/s40265-016-0645-5 · Cited by 26
“Metabolism and elimination data from healthy volunteers suggest that the liver does not extensively metabolize paliperidone, as 59 % of a 1 mg oral dose of radiolabelled paliperidone was eliminated unchanged in the urine [17].”
BackgroundInfluentialVasudev, A., Chaudhari, S., Sethi, R., Fu, R., Sandieson, R. M., & Forester, B. P. (2018) · Drugs & Aging · doi:10.1007/s40266-018-0579-6 · Cited by 26
Xu, H., Zhao, L., Pan, H., Zhang, Z., Liu, D., Tian, B., Shi-lin, M., Song, S., & Pan, W.-S. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.09.031 · Cited by 25
Suzuki, Y., Tsuneyama, N., Fukui, N., Sugai, T., Watanabe, J., Ono, S., Saito, M., Inoue, Y., & Someya, T. (2014) · The Pharmacogenomics Journal · doi:10.1038/tpj.2014.6 · Cited by 24
Invega Trinza: The First Four-Times-a-Year, Long-Acting Injectable Antipsychotic Agent.
Daghistani, N., & Rey, J. A. (2016) · PubMed Central · Cited by 25
Magnusson, M. O., Samtani, M. N., Plan, E. L., Jonsson, E. N., Rossenu, S., Vermeulen, A., & Russu, A. (2017) · CNS Drugs · doi:10.1007/s40263-017-0416-1 · Cited by 25
Interaction Between Paliperidone and Carbamazepine
Yasui‐Furukori, N., Kubo, K., Ishioka, M., Tsuchimine, S., & Inoue, Y. (2013) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e3182966c2f · Cited by 24
“ment of these 2 cytochrome P450 forms in the metabolism of paliperidone.(1,3) However, a preliminary study showed that”
BackgroundInfluentialde León, J. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000093 · Cited by 22
The preclinical discovery and development of paliperidone for the treatment of schizophrenia
Wesołowska, A., Jastrzębska‐Więsek, M., Cios, A., & Partyka, A. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1682994 · Cited by 22
“In rats, paliperidone was mostly metabolized by alicyclic hydroxylation, oxidative N-dealkylation, and benzisoxazole scission [17].”
BackgroundKerbusch‐Herben, V., Cleton, A., Berwaerts, J., Vandebosch, A., & Remmerie, B. M. M. (2014) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.122 · Cited by 22
“Paliperidone was also eliminated through four primary metabolic pathways: N-dealkylation (CYP3A4mediated process), monohydroxylation (CYP2D6-mediated process), alcohol dehydrogenation (non-CYP-mediated), and benzisoxazole scission (non-CYP-mediated).(12) Each of the individual metabolites accounted for up to a maximum…”
BackgroundMethodInfluentialSelf-citationThe preclinical discovery and development of cariprazine for the treatment of schizophrenia
Wesołowska, A., Partyka, A., Jastrzębska‐Więsek, M., & Kołaczkowski, M. (2018) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2018.1471057 · Cited by 22
Psychopharmacologic Treatment of Schizophrenia in Adolescents and Children
Lee, E. S., Kronsberg, H., & Findling, R. L. (2019) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2019.08.009 · Cited by 23
The pharmacology and formulation of paliperidone extended release
Chue, P. S., MacKenzie, E. M., Chue, J., & Baker, G. B. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.138 · Cited by 21
Savitz, A. J., Lane, R., Nuamah, I. F., Singh, J. B., Hough, D. W., & Gopal, S. (2015) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2014.0130 · Cited by 21
“Pali-peridone ER is primarily eliminated via renal excretion, potentially leading to fewer drug–drug interactions as opposed to risperidone, which is extensively metabolized in the liver (Vermeir et al. 2008; RISPERDAL (cid:2) prescribing information 2005).”
CYP450 and Its Implications in the Clinical Use of Antipsychotic Drugs
Molina, F. M. J. D. (2015) · Clinical and Experimental Pharmacology · doi:10.4172/2161-1459.1000176 · Cited by 21
“There are additional properties in terms of its lower protein binding and decreased inhibition of P-glycoprotein that lead to a decreased potential for drug-drug interactions [67,68,70].”
Backgroundde León, J. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000115 · Cited by 20
“The authors concluded that paliperidone is not extensively metabolized and is primarily excreted renally.(21) A comparative review written by the company researchers(20) provides a more accurate description of this isotope paliperidone study.”
Sliwa, J. K., Bossie, C. A., Ma, Y.-W., & Alphs, L. D. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.06.016 · Cited by 20
“The pharmacologically active entity (paliperidone) is metabolized via 4 primary pathways each metabolizing b10% of the total dose with the remaining59% excreted unchanged in the urine (Vermeir et al., 2008).”
BackgroundHart, X. M., Gründer, G., Unterecker, S., Schoretsanitis, G., Hiemke, C., Adamovic, I., Amann, F., Baumann, P., Bergemann, N., Brandt, C., et al. (2026) · Pharmacopsychiatry · doi:10.1055/a-2860-7861 · Cited by 20
Role of paliperidone extended-release in treatment of schizoaffective disorder
Canuso, C. M. (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s12612 · Cited by 19
Suzuki, H., Gen, K., Inoue, Y., Hibino, H., Mikami, A. S., Matsumoto, H., & Mikami, K. (2013) · International Journal of Psychiatry in Clinical Practice · doi:10.3109/13651501.2013.845218 · Cited by 19
“On average, each of these metabolites accounts for less than 5% of total excretion; approximately 60% of PAL is excreted directly from the kidneys (Vermeir et al. 2008).”
Background1,2-Benzisoxazole compounds: a patent review (2009 – 2014)
Uto, Y. (2015) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2015.1027192 · Cited by 19
“5 Deuterated compounds According to the investigation on the metabolism of paliperidone, particular C--H bonds have been found to be subject to the oxidative metabolism by human CYP enzymes [49].”
BackgroundPharmacokinetics and tolerability of paliperidone palmitate injection in Chinese subjects
Si, T., Su, Y., Liu, Y., Zhang, H., Li, H., Rui, Q., & Shu, L. (2014) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2388 · Cited by 18
“Other than renal excretion, four metabolic pathways were involved in the elimination of paliperidone, including CYP3A4 and CYP2D6 enzymes, each of which accounted for up to 6.5% of the administered dose (Vermeir et al., 2008).”
BackgroundInfluentialWong, Y. C., Centanni, M., & de Lange, E. C. M. (2019) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1365 · Cited by 18
Jadhav, S. A., Landge, S. B., Choudhari, P. M., Solanki, P. V., Bembalkar, S. R., & Mathad, V. T. (2011) · Chromatography Research International · doi:10.4061/2011/256812 · Cited by 18
Remmerie, B. M. M., Ariyawansa, J., Meulder, M. D., Coppola, D., & Berwaerts, J. (2015) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.648 · Cited by 17
Self-citationAmatniek, J. C., Canuso, C. M., Deutsch, S. I., Henderson, D. C., Mao, L., Mikesell, C., Rodriguez, S., Sheehan, J. J., & Alphs, L. D. (2013) · Clinical Schizophrenia & Related Psychoses · doi:10.3371/csrp.amca.021513 · Cited by 17
Paliperidone palmitate injection for the acute and maintenance treatment of schizophrenia in adults
Bishop, J. R., Kim, Solari, & Weiden, P. J. (2012) · Patient Preference and Adherence · doi:10.2147/ppa.s20657 · Cited by 17
“5 In vitro studies in human liver microsomes revealed that paliperidone palmitate does not appreciably inhibit the metabolism of drugs metabolized by cytochrome P450 (CYP) isozymes and is not significantly metabolized by CYP1A2, CYP2A6, CPY2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CPY3A5.”
InfluentialZhang, T., Yang, Y., Zhao, X., Jia, J., Su, H., He, H., Gu, J., & Zhu, G. (2014) · CrystEngComm · doi:10.1039/c4ce00784k · Cited by 17
Spina, E., & Crupi, R. (2011) · Journal of Central Nervous System Disease · doi:10.4137/jcnsd.s1607 · Cited by 17
Single‐dose pharmacokinetics of paliperidone extended‐release tablets in healthy Chinese subjects
Si, T., Shu, L., Liu, Y., Su, Y., Chunmei, G., & Hongyan, Z. (2010) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1132 · Cited by 16
“There is no relationship between the genotypic expression of metabolizing enzymes UGT1A1 and UGT1A6 and paliperidone pharmacokinetics(Vermeir et al., 2008).”
Yang, L. P. H. (2011) · CNS Drugs · doi:10.2165/11207440-000000000-00000 · Cited by 16
Xiamuxi, H., Wang, Z., Li, J., Wang, Y., Wu, C., Yang, F., Jiang, X., Liu, Y., Zhao, Q., Chen, W., et al. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.07.040 · Cited by 16
Schoretsanitis, G., Meyer, J. M., Conca, A., & Hiemke, C. (2023) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2023.2220962 · Cited by 15
“Oral paliperidone undergoes hepatic metabolism to a limited extend with one-fourth being catalyzed by CYP3A4; the rest is eliminated unchanged in urine [76].”
BackgroundInfluence of CYP2C19 and CYP2D6 on side effects of aripiprazole and risperidone: A systematic review
Brabander, E. Y. D., Schaars, K. K., van Amelsvoort, T., Budde, M., Heilbronner, U., Young, A. H., Juruena, M. F., Vieta, E., Fares‐Otero, N. E., Kas, M. J., et al. (2024) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2024.04.001 · Cited by 15
Taylor, K., & Elliott, S. P. (2013) · Drug Testing and Analysis · doi:10.1002/dta.1503 · Cited by 15
Baumann, P., & Hiemke, C. (2012) · doi:10.1002/9783527630905.ch11 · Cited by 15
Peuskens, J., Rubio, G., & Schreiner, A. (2014) · Annals of General Psychiatry · doi:10.1186/1744-859x-13-10 · Cited by 14
“Paliperidone ER is not expected to cause clinically important hepatic PK interactions with drugs that are metabolized by cytochrome P450 isozymes [75].”
BackgroundCanuso, C. M., & Battisti, W. P. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2010.495387 · Cited by 14
“Unlike risperidone and several other atypical antipsychotics, CYP2D6 and CYP3A4 isozymes seem to be minimally involved with paliperidone’s metabolism [25].”
BackgroundClinically Important Differences in the Pharmacokinetics of the Ten Newer “Atypical” Antipsychotics
Preskorn, S. (2012) · Journal of Psychiatric Practice · doi:10.1097/01.pra.0000419820.68128.ad · Cited by 14
Suzuki, H., Gen, K., Otomo, M., Inoue, Y., Hibino, H., Mikami, A. S., Matsumoto, H., & Mikami, K. (2014) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2393 · Cited by 14
“PAL is considered to be less affected by individual differences in metabolism than risperidone and to have less risk for interactions with other drugs (Vermeir et al., 2008).”
BackgroundMicrobial impacts in postmortem toxicology
Castle, J. W., Butzbach, D. M., Walker, G., Lenehan, C. E., Reith, F., & Kirkbride, K. P. (2017) · doi:10.1002/9781119062585.ch9 · Cited by 14
Suzuki, H., Gen, K., Otomo, M., Inoue, Y., Hibino, H., Mikami, A. S., Matsumoto, H., & Mikami, K. (2013) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12026 · Cited by 13
“It is thought that PAL is less likely to be affected by inter-individual differences in metabolism than risperidone, and to present less risk of drug–drug interactions.(3) The creation of an osmotic pump extended-release formulation that continually releases the drug at a constant rate over a period of 24 h, moreover,…”
BackgroundMahdy, W. Y. B., Yamamoto, K., Ito, T., Fujiwara, N., Fujioka, K., Horai, T., Otsuka, I., Imafuku, H., Omura, T., Iijima, K., et al. (2023) · Clinical and Translational Science · doi:10.1111/cts.13473 · Cited by 12
Krishna, M. V., Nellutla, A., Gorrepati, M., Majeti, S., & Mamidala, S. K. (2015) · Annales Pharmaceutiques Françaises · doi:10.1016/j.pharma.2015.04.002 · Cited by 12
Rub, R. A., Beg, S., Kazmi, I. A., Afzal, O., Almalki, W. H., Alghamdi, S. A., Akhter, S., Ali, A., & Ahmed, F. J. (2020) · Journal of Chromatography B · doi:10.1016/j.jchromb.2020.122433 · Cited by 12
Boyda, H. N., Procyshyn, R. M., Tse, L., Yuen, J. W. Y., Honer, W. G., & Barr, A. M. (2021) · PLoS ONE · doi:10.1371/journal.pone.0246211 · Cited by 12
“Paliperidone, by contrast, is predominantly excreted unchanged in the urine [91].”
BackgroundJudson, P. N., Long, A., Murray, E. J., & Patel, M. L. (2015) · Molecular Informatics · doi:10.1002/minf.201400184 · Cited by 11
Pharmacokinetic drug evaluation of paliperidone in the treatment of schizoaffective disorder
Macaluso, M., Oliver, H., & Sohail, Z. (2017) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1351546 · Cited by 11
Chen, H., Zhao, L., Li, G., Leng, D., Ma, P., Lijin, T., & Zhang, T. (2014) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2014.07.008 · Cited by 11
Escitalopram-induced liver injury: A case report and review of literature
Ng, Q. X., Yong, C. S. K., Loke, W., Yeo, W. S., & Soh, A. Y. S. (2019) · World Journal of Hepatology · doi:10.4254/wjh.v11.i10.719 · Cited by 11
Schoretsanitis, G., Haen, E., Conca, A., Piacentino, D., Ridders, F., Hiemke, C., Gründer, G., & Paulzen, M. (2020) · Pharmacopsychiatry · doi:10.1055/a-1221-5293 · Cited by 9
“5 % of the absorbed paliperidone [27, 40], and most of it is excreted unchanged [25].”
BackgroundPaliperidone in the treatment of delirium: results of a prospective open-label pilot trial
Yoon, H.-K., Kim, Y., Han, C., Ko, Y., Lee, H., Kwon, D., & Kim, L. (2011) · Acta Neuropsychiatrica · doi:10.1111/j.1601-5215.2011.00568.x · Cited by 9
“About half of the renal excretion occurred by active secretion (27).”
BackgroundPaliperidone for the Treatment of Ketamine-Induced Psychosis: A Case Report
Zuccoli, M. L., Muscella, A., Fucile, C., Carrozzino, R., Mattioli, F., Martelli, A., & Orengo, S. (2014) · The International Journal of Psychiatry in Medicine · doi:10.2190/pm.48.2.c · Cited by 9
“In vitro studies showed that paliperidone is mostly excreted unchanged in urine, being for only a very small fraction metabolized by two isozymes, CYP 2D6 and 3A4 [18].”
BackgroundSawant, S. D., & Barge, V. (2013) · Journal of Pharmacy Research · doi:10.1016/j.jopr.2012.11.011 · Cited by 9
Paliperidone Induced Hypoglycemia by Increasing Insulin Secretion
Omi, T., Riku, K., Fukumoto, M., Kanai, K., Omura, Y., Takada, H., & Matunaga, H. (2016) · Case Reports in Psychiatry · doi:10.1155/2016/1805414 · Cited by 9
Identification of postmortem paliperidone metabolite in human blood by LC–Q-Orbitrap-MS
Yamagishi, Y., Inokuchi, G., Hoshioka, Y., Nagasawa, S., Iwase, H., & Ogra, Y. (2023) · Journal of Analytical Toxicology · doi:10.1093/jat/bkad033 · Cited by 9
Božina, N., Jovanović, N., Lovrić, M., & Medved, V. (2008) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e3181896afc · Cited by 9
“Its active metabolite 9-hydroxyrisperidone (9-OHrisperidone) is approximately equipotent with the parent drug in dopamine receptor affinity and has been recently approved as the new antipsychotic drug called paliperidone.(2) The entire risperidone active moiety (risperidone plus 9-OH-risperidone) is regarded to contri…”
BackgroundFagiolini, A. M., Casamassima, F., Mostacciuolo, W., Forgione, R. N., Goracci, A., & Goldstein, B. I. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2010.490831 · Cited by 9
“Paliperidone is excreted unchanged through kidneys with minimal hepatic metabolism [86].”
BackgroundRussu, A., Savitz, A., Mathews, M., Gopal, S., Feng, Y., & Samtani, M. N. (2019) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001137 · Cited by 8
“Following administration of a single oral dose of 1 mg immediate-release (IR) (14)C-paliperidone, 59% of the dosewas excreted unchanged into urinewithin 1week, indicating that paliperidone is not extensively metabolized in the liver.(14) Approximately 80% of the administered radioactivity was recovered in urine and 11…”
BackgroundZhao, J., Cai, S., Lu, H., Bai, Z., & Wu, R. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s84833 · Cited by 8
“Paliperidone ER is less prone to hepatic drug-drug interactions due to the lack of cytochrome P450 inhibition and less hepatic metabolism.(9) As a result, there is only a small reduction in total exposure to paliperidone ER in patients with hepatic impairment.”
Systemic Inflammation Complicates the Interpretation of Therapeutic Drug Monitoring of Risperidone
Helland, A., Habib, S., Ulvestad, L., & Spigset, O. (2018) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000873 · Cited by 8
Metadata
- Authors
- Vermeir, M., Naessens, I., Remmerie, B., Mannens, G., Hendrickx, J., Sterkens, P., Talluri, K., Boom, S., Eerdekens, M., van Osselaer, N., & Cleton, A.
- Affiliations
- Janssen (Belgium) (BE)
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 36
- Issue
- 4
- Pages
- 769-779
- ISSN
- 0090-9556 (ISSN-L)
- OpenAlex
- W2127872656
- Cited by
- 158
- References
- 16
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 9 · 2015: 8 · 2014: 13 · 2013: 16 · 2012: 14
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism and Disposition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- paliperidone, pharmacokinetics, drug metabolism, renal excretion, atypical antipsychotics, CYP2D6 polymorphism, N-dealkylation, glucuronidation, metabolites
- MeSH terms
- Paliperidone Palmitate, Adult, Feces, Humans, Intestinal Absorption, Isoxazoles, Kidney, Liver, Male, Middle Aged, Pyrimidines, Time Factors, Biogenic Monoamines, Metabolic Networks and Pathways
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
