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Cited by 23Rheumatoid Arthritis Research and TherapiesBiosimilars and Bioanalytical MethodsMonoclonal and Polyclonal Antibodies Research

The DOI matches its Crossref record.

Pharmacokinetics and pharmacodynamics of single subcutaneous doses of tocilizumab administered with or without rHuPH20

Morcos, Peter N., Zhang, Xiaoping, McIntyre, Christine, Bittner, Beate, Rowell, Lucy, Hussain, Zubair·2013·Int. Journal of Clinical Pharmacology and Therapeutics
DOI 10.5414/cp201847
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Abstract

OBJECTIVES: To investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tocilizumab with and without rHuPH20 (a recombinant human hyaluronidase) in healthy volunteers. METHODS: This was an open-label, single ascending dose study. Subjects were assigned to tocilizumab 162 mg or tocilizumab 162, 324, or 648 mg plus rHuPH20. PK and PD samples were collected after dosing and were estimated with non-compartmental methods. Geometric mean ratio (GMR) for area under the plasma concentration-time curve from zero to infinity (AUC0-∞) and (maximum serum concentration) Cmax with and without rHuPH20 was estimated using one-way analysis of variance. Safety and tolerability were monitored throughout the study. RESULTS: 48 subjects (12/cohort) received a single dose of tocilizumab with or without rHuPH20. For tocilizumab 162 mg, tocilizumab 162 mg/rHuPH20, tocilizumab 324 mg/rHuPH20, and tocilizumab 648 mg/rHuPH20, mean ± SD tocilizumab PK parameters were 2,510 ± 1,060, 2,860 ± 468, 10,800 ± 3,220, and 29,900 ± 5,280 μg×h/ml for AUC0-∞; 11.5 ± 3.7, 16.2 ± 2.8, 43.8 ± 12.4, and 77.8 ± 14.5 μg/ml for Cmax; and 89.1 ± 41.1, 54.0 ± 19.5, 66.0 ± 26.8, and 86.1 ± 50.6 h for tmax, respectively. Coadministration of tocilizumab 162 mg with rHuPH20 resulted in slightly increased exposure: GMR (90% confidence interval) for AUC0-∞, 1.20 (1.00 - 1.44) and Cmax, 1.45 (1.24 - 1.70). Increasing tocilizumab doses resulted in significant deviation from dose proportionality for tocilizumab Cmax (p = 0.0057) and AUC0-∞ (p < 0.0001). Changes in interleukin-6, soluble interleukin- 6 receptor, and C-reactive protein were also dose dependent and similar with and without rHuPH20. CONCLUSIONS: Tocilizumab in combination with rHuPH20 resulted in slightly increased tocilizumab exposure compared with tocilizumab alone, whereas PD markers were comparable. Subcutaneous administration of tocilizumab with rHuPH20 was well tolerated.

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  • Coadministration of hyaluronidase with tocilizumab in healthy volunteers slightly increased tocilizumab exposure compared with administration without hyaluronidase.

    “In a study of tocilizumab in healthy volunteers, coadministration of hyaluronidase resulted in a slightly increased tocilizumab exposure, a trend towards lower pharmacokinetic variability, and earlier Tmax compared with administration without hyaluronidase [90].”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [90]

  • Coadministration of hyaluronidase with tocilizumab in healthy volunteers resulted in earlier Tmax compared with administration without hyaluronidase.

    “In a study of tocilizumab in healthy volunteers, coadministration of hyaluronidase resulted in a slightly increased tocilizumab exposure, a trend towards lower pharmacokinetic variability, and earlier Tmax compared with administration without hyaluronidase [90].”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [90]

  • Coadministration of hyaluronidase with tocilizumab in healthy volunteers showed a trend towards lower pharmacokinetic variability compared with administration without hyaluronidase.

    “In a study of tocilizumab in healthy volunteers, coadministration of hyaluronidase resulted in a slightly increased tocilizumab exposure, a trend towards lower pharmacokinetic variability, and earlier Tmax compared with administration without hyaluronidase [90].”

    From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [90]

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Metadata

Authors
Morcos, P. N., Zhang, X., McIntyre, C., Bittner, B., Rowell, L., & Hussain, Z.
Affiliations
F. Hoffmann-La Roche AG (CH)
ORCID
Venue
Int. Journal of Clinical Pharmacology and Therapeutics
Publisher
Dustri-Verlgag Dr. Karl Feistle
Published
2013-07-01
Volume
51
Issue
07
Pages
537-548
ISSN
0946-1965 (ISSN-L)
DOI
10.5414/cp201847
OpenAlex
W1990376387
Cited by
23
References
0
Citations by year
2025: 1 · 2024: 3 · 2023: 4 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 3 · 2015: 3 · 2013: 1
FWCI
1.09
Type
journal article
Language
en
Open access
closed
Locations
  • International Journal of Clinical Pharmacology and Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
tocilizumab, rHuPH20, recombinant human hyaluronidase, pharmacokinetics, pharmacodynamics, subcutaneous administration, drug-drug interactions, drug exposure, healthy volunteers, safety and tolerability, IL-6 receptor inhibitor, single ascending dose, dose proportionality, adverse events, injection site reactions
MeSH terms
Adult, C-Reactive Protein, Drug Interactions, Female, Humans, Hyaluronoglucosaminidase, Injections, Subcutaneous, Male, Metabolic Clearance Rate, Middle Aged, Models, Biological, Recombinant Proteins, Models, Statistical, Biomarkers, Interleukin-6, Antirheumatic Agents, Inflammation Mediators, Area Under Curve, Receptors, Interleukin-6, Young Adult, Antibodies, Monoclonal, Humanized

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