Safety, tolerability and pharmacokinetics of rilpivirine following administration of a long‐acting formulation in healthy volunteers
Abstract
Objectives: This phase I healthy volunteer study (NCT01031589) was carried out to investigate the safety/tolerability and pharmacokinetics of a rilpivirine (RPV; TMC278) long‐acting (LA) formulation after single and multiple intramuscular (IM) injections. Methods: I n the first part of the study, which had an open‐label design, a single RPV LA IM injection (300 mg/mL) of 300 (n = 6) or 600 (n = 5) mg was given to the volunteers. In the second part of the study, which had a double‐blind, randomized, placebo‐controlled design, three RPV LA IM injections (one every 4 weeks) at 1200/600/600 mg (n = 6) or placebo (n = 2) were given. Safety and local tolerability were monitored. RPV plasma concentrations were analysed up to 28 days after injection or until they were < 20 ng/mL. Results: Grade 1/2 RPV‐related adverse events in the 300, 600 and 1200/600/600 mg groups were: rash (zero, one and one subject, respectively, the last of whom discontinued participation in the study); musculoskeletal stiffness (three, zero and zero subjects, respectively); injection site reactions (one, two and two subjects, respectively). After one injection of 300, 600 or 1200 mg RPV LA, the mean (standard deviation) maximum plasma concentration was 39 (25), 48 (13) and 140 (16) ng/mL, and the mean (standard deviation) area under the concentration–time curve (28 days) was 17 090 (8907), 25 240 (8184) and 55 350 (13 550) ng h/mL, respectively. RPV pharmacokinetics were largely comparable after the 1200 mg loading dose and both 600 mg injections of RPV LA. The mean (standard deviation) RPV plasma concentration across the 28‐day dosing interval after the last injection in the 1200/600/600 mg group was 79 (19) ng/mL. Conclusions: Single and multiple IM injections of RPV LA demonstrated favourable local/systemic tolerability in healthy volunteers. RPV pharmacokinetics suggested that clinically relevant plasma concentrations can be achieved with this LA formulation.
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?
Estimated half-lives of rilpivirine and cabotegravir in nanosuspensions were 44-61 days and 25-54 days, respectively, enabling administration every 1-3 months.
“Estimated half-lives of rilpivirine and cabotegravir in nanosuspensions were 44-61 days (ref. 91 ) and 25-54 days (ref. 91 ), respectively, enabling administration every 1-3 months.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [91]
Half-lives of rilpivirine and cabotegravir in tablets have been estimated to be ~1-2 days.
“In contrast, half-lives of rilpivirine and cabotegravir in tablets have been estimated to be ~1-2 days (refs. 91,92 ).”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [91]
Cites
Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents
(1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-12_part_2-199806151-00003 · Cited by 5,197 · see citing works
Molina, J., Cahn, P. E., Grinsztejn, B. G. J., Lazzarin, A., Mills, A., Saag, M. S., Supparatpinyo, K., Walmsley, S. L., Crauwels, H. M., Rimsky, L. T., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60936-7 · Cited by 404 · see citing works
Self-citationCohen, C. J., Andrade-Villanueva, J. F., Clotet, B., Fourie, J., Johnson, M. A., Ruxrungtham, K., Wu, H., Zorrilla, C., Crauwels, H. M., Rimsky, L. T., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60983-5 · Cited by 373 · see citing works
Self-citationLong-acting injectable antiretrovirals for HIV treatment and prevention
Spreen, W. R., Margolis, D. A., & Pottage, J. C. (2013) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000002 · Cited by 247 · see citing works
Baert, L., Klooster, G. A. E. V. '., Dries, W., François, M., Wouters, A., Basstanie, E. D., Iterbeke, K., Stappers, F., Stevens, P., Schueller, L., et al. (2009) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2009.03.006 · Cited by 224 · see citing works
Klooster, G. A. E. V. '., Hoeben, E., Borghys, H., Looszova, A., Bouche, M.-P. L. A., Velsen, F. V., & Baert, L. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01529-09 · Cited by 186 · see citing works
Cohen, C. J., Molina, J., Cahn, P. E., Clotet, B., Fourie, J., Grinsztejn, B. G. J., Wu, H., Johnson, M. A., Saag, M. S., Supparatpinyo, K., et al. (2012) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e31824d006e · Cited by 157 · see citing works
Self-citationCohen, C. J., Molina, J., Cassetti, I., Chetchotisakd, P., Lazzarin, A., Orkin, C. M., Rhame, F. S., Stellbrink, H.-J., Li, T., Crauwels, H. M., et al. (2012) · AIDS · doi:10.1097/qad.0b013e32835cee6e · Cited by 139 · see citing works
Self-citationNanotechnology and the Treatment of HIV Infection
Parboosing, R., Maguire, G. E. M., Govender, P., & Kruger, H. G. (2012) · Viruses · doi:10.3390/v4040488 · Cited by 130 · see citing works
Jackson, A., Else, L., Mesquita, P. M. M., Egan, D., Back, D. J., Karolia, Z., Ringner-Nackter, L., Higgs, C., Herold, B. C., Gazzard, B., et al. (2014) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2014.118 · Cited by 106 · see citing works
Williams, J. K., Sayles, H. R., Meza, J. L., Sayre, P., Sandkovsky, U., Gendelman, H. E., Flexner, C. W., & Swindells, S. (2013) · Nanomedicine · doi:10.2217/nnm.12.214 · Cited by 104 · see citing works
McDonald, T. O., Giardiello, M., Martin, P., Siccardi, M., Liptrott, N. J., Smith, D., Roberts, P., Curley, P., Schipani, A., Khoo, S., et al. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201300280 · Cited by 90 · see citing works
Ford, S. L., Gould, E., Chen, S., Margolis, D., Spreen, W., Crauwels, H., & Piscitelli, S. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01235-13 · Cited by 83 · see citing works
Self-citationThe Pharmacokinetics of Long-Acting Antipsychotic Medications
Spanarello, S., & Ferla, T. (2014) · Current Clinical Pharmacology · doi:10.2174/15748847113089990051 · Cited by 70 · see citing works
Bennett, D., Jordan, M. R., Bertagnolio, S., et al. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis207 · Cited by 67 · see citing works
The promise of pre-exposure prophylaxis with antiretroviral drugs to prevent HIV transmission
Hankins, C. A., & Dybul, M. R. (2012) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e32835b809d · Cited by 59 · see citing works
Kanmogne, G. D., Kanmogne, G. D., Singh, S., Roy, U. B., Liu, X., McMillan, Gorantla, Balkundi, Zhou, Y., Alnouti, et al. (2012) · International Journal of Nanomedicine · doi:10.2147/ijn.s29454 · Cited by 56 · see citing works
Impact of Food and Different Meal Types on the Pharmacokinetics of Rilpivirine
Crauwels, H. M., van Heeswijk, R. P. G., Buelens, A., et al. (2013) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.107 · Cited by 52 · see citing works
Self-citationDraper, B., Morroni, C., Hoffman, M. N., et al. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005214.pub2 · Cited by 45 · see citing works
Crauwels, H., van Schaick, E., Heeswijk, R. G. V., et al. (2010) · Journal of the International AIDS Society · doi:10.1186/1758-2652-13-s4-p186 · Cited by 23 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Nanotechnology approaches for global infectious diseases
Kirtane, A. R., Verma, M., Karandikar, P., Furin, J., Langer, R., & Traverso, G. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00866-8 · Cited by 520 · see citing works
- Authors
- Verloes, R., Deleu, S., Niemeijer, N., Crauwels, H., Meyvisch, P., & Williams, P.
- Affiliations
- Janssen (Belgium) (BE)
- Corresponding author
- Verloes, R
- Venue
- HIV Medicine
- Publisher
- Wiley
- Published
- 2015-05-18
- Volume
- 16
- Issue
- 8
- Pages
- 477-484
- ISSN
- 1464-2662 (ISSN-L)
- 1468-1293
- OpenAlex
- W1866224665
- Cited by
- 50
- References
- 20
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 3
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- HIV Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
- Keywords
- rilpivirine, long-acting formulations, intramuscular injection, pharmacokinetics, safety and tolerability, HIV antiretroviral therapy, plasma concentration, loading dose, adverse events, injection site reactions, antiviral drug delivery, healthy volunteers, dosing interval, HIV-1 reverse transcriptase inhibitors
- MeSH terms
- Rilpivirine, Adult, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Male, Middle Aged, HIV Infections, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Area Under Curve, Young Adult, Healthy Volunteers
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
