Population pharmacokinetic modeling and simulation to guide dose selection for RBP‐7000, a new sustained‐release formulation of risperidone
Abstract
RBP‐7000 is a long‐acting formulation of risperidone designed for once‐monthly subcutaneous injection for the treatment of schizophrenia. The objective was to estimate clinically effective doses of RBP‐7000 based on model simulations and on the comparison with other long‐acting injectable antipsychotics. A population pharmacokinetic model of RBP‐7000 was developed in 90 clinically stable schizophrenic patients having received single/repeated doses of 60, 90, or 120 mg. Model simulations were conducted to compare active moiety plasma exposure after repeated RBP‐7000 administrations to the published data of long‐acting risperidone injection (Risperdal® Consta®) at 25 and 50 mg, and of paliperidone palmitate (Invega® Sustenna®) at 50 and 100 mg equivalent paliperidone. Predictions of dopamine D2 receptor occupancy were derived from the simulated active moiety concentrations. Simulations showed similar active moiety plasma exposure at steady‐state for 90 mg of RBP‐7000 and 25 mg of long‐acting risperidone. In comparison to risperidone, RBP‐7000 reached effective concentrations immediately after the first administration. RBP‐7000 at the doses of 60 and 90 mg provided similar active moiety plasma concentrations at steady‐state compared to 50 and 100 mg equivalent paliperidone, respectively. These findings provide guidance for dose selection in Phase III clinical trials and suggest potential benefits for RBP‐7000 over competitors.
Integrity signals
Registry
Cites
Statistics
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?
A more recent formulation of LAI risperidone provides sustained release of risperidone once monthly via abdominal subcutaneous injection (RLAI-polymer).
“A more recent formulation of LAI risperidone provides sustained release of risperidone once monthly via abdominal subcutaneous injection (RLAI-polymer) [90, 91].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [91]
The biodegradable implant of RLAI-polymer then delivers risperidone in a controlled fashion.
“The biodegradable implant then delivers risperidone in a controlled fashion [91].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [91]
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Compliance With Medication Regimens for Mental and Physical Disorders
Cramer, J. A., & Rosenheck, R. (1998) · Psychiatric Services · doi:10.1176/ps.49.2.196 · Cited by 725 · see citing works
Predictors of Noncompliance in Patients With Schizophrenia
Perkins, D. O. (2002) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v63n1206 · Cited by 546 · see citing works
Savić, R. M., Jonker, D. M., Kerbusch, T., & Karlsson, M. O. (2007) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-007-9066-0 · Cited by 503 · see citing works
Kane, J. M., Eerdekens, M., Lindenmayer, J., Keith, S. J., Lesem, M. D., & Karcher, K. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.6.1125 · Cited by 489 · see citing works
Hicks, J. K., Swen, J. J., Thorn, C. F., Sangkuhl, K., Kharasch, E. D., Ellingrod, V. L., Skaar, T. C., Müller, D., Gaedigk, A., & Stingl, J. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2013.2 · Cited by 454 · see citing works
de León, J., Susce, M. T., Pan, R.-M., Fairchild, M., Koch, W. H., & Wedlund, P. J. (2005) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v66n0103 · Cited by 319 · see citing works
Huang, M., Peer, A. V., Woestenborghs, R. J. H., Coster, R. D., Heykants, J., Jansen, A. A. I., Żylicz, Z., Visscher, H. W., & Jonkman, J. H. G. (1993) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1993.146 · Cited by 316 · see citing works
Treatment of Schizophrenia With Long-Acting Injectable Risperidone
Fleischhacker, W. W., Eerdekens, M., Karcher, K., Remington, G. J., Llorca, P., Chrzanowski, W., Martin, S. D., & Gefvert, O. (2003) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v64n1017 · Cited by 288 · see citing works
Absorption, 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 · see citing works
Factors influencing relapse in the long-term course of schizophrenia
Ayuso-Gutiérrez, J. L., & Vega, J. M. D. R. (1997) · Schizophrenia Research · doi:10.1016/s0920-9964(97)00131-x · Cited by 203 · see citing works
Pharmacologic approach to management of agitation associated with dementia.
Heykants, J., Huang, M. L., Mannens, G., Meuldermans, W., Snoeck, E., Beijsterveldt, L. V., Peer, A. V., & Woestenborghs, R. (1994) · PubMed · Cited by 200 · see citing works
Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets
Chue, P. S., Eerdekens, M., Augustyns, I., Lachaux, B., Molčan, P., Eriksson, L., Pretorius, H., & David, A. S. (2004) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2004.07.003 · Cited by 197 · see citing works
Beijsterveldt, L. E. C. V., Geerts, R., Leysen, J. E., Megens, A. A. H. P., den Eynde, H. M. J. V., Meuldermans, W., & Heykants, J. J. P. (1994) · Psychopharmacology · doi:10.1007/bf02245444 · Cited by 177 · see citing works
Samtani, M. N., Vermeulen, A., & Stuyckens, K. (2009) · Clinical Pharmacokinetics · doi:10.2165/11316870-000000000-00000 · Cited by 170 · see citing works
Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia
Eerdekens, M., Hove, I. V., Remmerie, B. M. M., & Mannaert, E. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2003.11.001 · Cited by 161 · see citing works
A PET Study Evaluating Dopamine D2 Receptor Occupancy for Long-Acting Injectable Risperidone
Remington, G. J., Mamo, D. C., Labelle, A., Reiss, J. P., Shammi, C., Mannaert, E., Mann, S. W., & Kapur, S. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.3.396 · Cited by 114 · see citing works
Feng, Y., Pollock, B. G., Coley, K. C., Marder, S. R., Miller, D. D., Kirshner, M. A., Aravagiri, M., Schneider, L. S. S., & Bies, R. R. (2008) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2008.03276.x · Cited by 86 · see citing works
Antipsychotic efficacy: Relationship to optimal D2-receptor occupancy
Pani, L., Pira, L., & Marchese, G. (2007) · European Psychiatry · doi:10.1016/j.eurpsy.2007.02.005 · Cited by 78 · see citing works
Dosing 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 · see citing works
Long-Acting Injectable Risperidone for the Treatment of Schizophrenia
M??ller, H.-J. (2007) · Drugs · doi:10.2165/00003495-200767110-00003 · Cited by 58 · see citing works
Vermeulen, A., Piotrovsky, V., & Ludwig, E. A. (2006) · Journal of Pharmacokinetics and Pharmacodynamics · doi:10.1007/s10928-006-9040-2 · Cited by 57 · see citing works
Atrigel: A potential parenteral controlled drug delivery system
Malik, K., Singh, I., Nagpal, M., & Arora, E. (2010) · Der Pharmacia Sinica · Cited by 41 · see citing works
Gomeni, R., Heidbreder, C., Fudala, P. J., & Nasser, A. F. (2013) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.141 · Cited by 38 · see citing works
Self-citationChue, P. S. (2007) · Neuropsychiatric Disease and Treatment · doi:10.2147/nedt.2007.3.1.13 · Cited by 37 · see citing works
Keith, S. J. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.9.1.9 · Cited by 36 · see citing works
Laffont, C. M., Gomeni, R., Zheng, B., Heidbreder, C., Fudala, P. J., & Nasser, A. F. (2014) · Clinical Pharmacokinetics · doi:10.1007/s40262-014-0132-7 · Cited by 35 · see citing works
Self-citationCYP2D6 poor metabolizer status might be associated with better response to risperidone treatment
Almoguera, B., Riveiro-Álvarez, R., López‐Castromán, J., Dorado, P., Vaquero‐Lorenzo, C., Fernández‐Piqueras, J., LLerena, A., Abad‐Santos, F., Baca‐García, E., Dal‐Ré, R., et al. (2013) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e3283659a94 · Cited by 35 · see citing works
Long-acting risperidone injection
Love, R. C., & Conley, R. J. (2004) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/61.17.1792 · Cited by 29 · see citing works
Nucci, G., Goméni, R., & Poggesi, I. (2009) · Expert Opinion on Drug Discovery · doi:10.1517/17460440903036073 · Cited by 27 · see citing works
Gopal, S., Liu, Alphs, L. D., Savitz, Nuamah, I. F., & Hough, D. (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s49944 · Cited by 24 · see citing works
Regenthal, R., Künstler, U., Hesse, S., Sabri, O., & Preiss, R. (2005) · International Journal of Clinical Pharmacology and Therapeutics · doi:10.5414/cpp43370 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Schoretsanitis, G., Spina, E., Hiemke, C., & de León, J. (2017) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2017.1345623 · Cited by 94 · see citing works
de Leon, J. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.05.033 · Cited by 75 · see citing works
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 · see citing works
Jones, A. K., Ngaimisi, E., Gopalakrishnan, M., Young, M. A., & Laffont, C. M. (2021) · Clinical Pharmacokinetics · doi:10.1007/s40262-020-00957-0 · Cited by 53 · see citing works
Self-citationNasser, A. F., Henderson, D. C., D, M. F. M., Fudala, P. J., Twumasi‐Ankrah, P., Kouassi, A., & Heidbreder, C. A. (2016) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000479 · Cited by 53 · see citing works
Self-citationLaffont, C. M., Goméni, R., Heidbreder, C. A., Jones, J. P., & Nasser, A. F. (2015) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.665 · Cited by 50 · see citing works
Self-citationCitrome, L. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1371014 · Cited by 34 · see citing works
Isitt, J. J., Nadipelli, V. R., Kouassi, A., D, M. F. M., & Heidbreder, C. A. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.03.020 · Cited by 24 · see citing works
“RBP-7000 is the first once-monthly subcutaneous (SC) formulation of risperidone using the ATRIGEL® delivery system in late-stage clinical development (Gomeni et al., 2013; Laffont et al., 2014, 2015; Nasser et al., 2016).”
MethodSelf-citationIvaturi, V. D., Gopalakrishnan, M., Gobburu, J. V. S., Zhang, W., Liu, Y., Heidbreder, C. A., & Laffont, C. M. (2017) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13246 · Cited by 24 · see citing works
“org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY [1], and are permanently archived in the Concise Guide to PHARMACOLOGY 2015/16 [2-6].”
BackgroundSelf-citationEmerging pharmacological therapies in schizophrenia: what’s new, what’s different, what’s next?
Citrome, L. (2016) · CNS Spectrums · doi:10.1017/s1092852916000729 · Cited by 22 · see citing works
Newer Formulations of Risperidone: Role in the Management of Psychotic Disorders
Clark, I., & Taylor, D. M. (2020) · CNS Drugs · doi:10.1007/s40263-020-00735-3 · Cited by 17 · see citing works
Li, L., Tran, D. C., Zhu, H., Balimane, P. V., Willett, G. D., Zhao, P., Gerrard, S. E., Vogelsong, K. M., Wang, Y., & Seo, S. K. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-031120-015212 · Cited by 10 · see citing works
Applications of pharmacometrics in drug development
Xiong, Y., Samtani, M. N., & Ouellet, D. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115503 · Cited by 9 · see citing works
PerserisTM: A New and Long-Acting, Atypical Antipsychotic Drug-Delivery System.
Karas, A., Burdge, G., & Rey, J. A. (2019) · Europe PMC (PubMed Central) · Cited by 9 · see citing works
Vhora, I., Bardoliwala, D., Ranamalla, S. R., & Javia, A. (2019) · Springer eBooks · doi:10.1007/978-981-13-3642-3_7 · Cited by 8 · see citing works
Schizophrenia and Related Psychoses
(2021) · Wiley eBooks · doi:10.1002/9781119870203.mpg001 · Cited by 8 · see citing works
Tchobaniouk, L. V., McAllister, E., Bishop, D. L., Carpentier, R., Heins, K. R., Haight, R. J., & Bishop, J. R. (2020) · Patient Preference and Adherence · doi:10.2147/ppa.s192418 · Cited by 7 · see citing works
“Risperidone-SQ has two absorption peaks following injection, both of similar magnitude.(20,21) The first peak occurs 4 to 6 hrs post-injection as a result of an initial release of the risperidone from the depot.”
BackgroundInfluentialNewer Formulations of Risperidone: Remarks About Risperidone ISM®
Anta, L., Mata, E., & D., L. O. (2020) · CNS Drugs · doi:10.1007/s40263-020-00762-0 · Cited by 7 · see citing works
Renzulli, J., Tagawa, S. T., Atkinson, S. N., Boldt‐Houle, D. M., & Moul, J. W. (2020) · BJUI Compass · doi:10.1002/bco2.13 · Cited by 6 · see citing works
Wang, W., Wang, X., Dong, Y., Walling, D. P., Liu, P., Liu, W., Shi, Y., & Sun, K. (2024) · Neurology and Therapy · doi:10.1007/s40120-024-00578-w · Cited by 5 · see citing works
“Drug release of long-acting IM injection agents such as paliperidone palmitate or RBP-7000 (a new sustained-release formulation of risperidone) has been previously investigated and characterized in population PK models [13, 14].”
Population Pharmacokinetics of Risperidone and Paliperidone in Schizophrenia: A Systematic Review
Carrascosa-Arteaga, A., Nalda‐Molina, R., Más‐Serrano, P., & Ramón-López, A. (2025) · Pharmaceuticals · doi:10.3390/ph18050698 · Cited by 4 · see citing works
“These distinct features necessitated the development of complex PK models incorporating dual absorption processes: an initial rapid delivery from the SC injection site, followed by a slower release into the systemic circulation [47,51,52,57].”
Influentialde Filippis, R., D’Onofrio, E., Liparota, G., Scaramuzzino, A., Aguglia, A., Amerio, A., Serafini, G., & Fazio, P. D. (2025) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2025.2551636 · Cited by 2 · see citing works
“A newer formulation of LAI risperidone enables sustained, once-monthly drug release through subcutaneous administration in the abdominal region with a subcutaneous injection (RSQ), also known as 2-syringe mixing system suspension polymer [89,90].”
Prescribing LAIs: from completing the first injection to going steady
Cutler, A. J., & Grady, M. M. (2025) · CNS Spectrums · doi:10.1017/s1092852925100588 · Cited by 1 · see citing works
Risperidone Oral and Long-Acting Injectable; Paliperidone Oral and Long-Acting Injectable
Meyer, J. M., & Stahl, S. M. (2021) · Cambridge University Press eBooks · doi:10.1017/9781009002103.017
Lv, D., Li, S., Li, Y., Lin, M., Zhai, Y., Wu, M., Qiu, Y., Zhao, Q. D., & Liu, J. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s517282
- Authors
- Laffont, C. M., Gomeni, R., Zheng, B., Heidbreder, C., Fudala, P. J., & Nasser, A. F.
- Affiliations
- Pharmacometrica La Fouillade France
- Alleantis Research Triangle Park NC 27709 USA
- Reckitt Benckiser (United States) (US)
- Corresponding author
- Zheng, Bo
- Venue
- The Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2014-07-23
- Volume
- 55
- Issue
- 1
- Pages
- 93-103
- ISSN
- 0021-9754 (ISSN-L)
- 0091-2700
- 1552-4604
- OpenAlex
- W1972479462
- Cited by
- 26
- References
- 32
- Citations by year
- 2025: 4 · 2024: 2 · 2021: 3 · 2020: 6 · 2019: 3 · 2017: 3 · 2016: 4 · 2015: 1
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- risperidone, long-acting injectable antipsychotics, sustained-release formulation, subcutaneous injection, schizophrenia, dose selection, population pharmacokinetic model, plasma exposure, dopamine D2 receptor occupancy, paliperidone palmitate, Risperdal Consta, model simulation
- MeSH terms
- Paliperidone Palmitate, Adult, Delayed-Action Preparations, Female, Humans, Isoxazoles, Male, Middle Aged, Models, Biological, Palmitates, Pyrimidines, Antipsychotic Agents, Risperidone
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
