Safety and pharmacokinetics of recombinant human relaxin in systemic sclerosis.

Abstract

OBJECTIVE:

To investigate the safety and pharmacokinetics of a 28 day continuous subcutaneous infusion of recombinant human relaxin in patients with systemic sclerosis with diffuse scleroderma.

METHODS:

Thirty patients with stable diffuse scleroderma of moderate severity received recombinant human relaxin at 6, 12, 50, 100, and 200 microg/kg/day or placebo in a double blind, sequential panel, dose escalation study.

RESULTS:

All patients completed 28 days of study treatment. Steady state concentrations of serum relaxin were achieved by the 3rd day of infusion and were dose proportionate. Patients receiving 200 microg/kg/day achieved levels about 50-fold those of normal pregnancy. Pharmacokinetics of relaxin were nonlinear with hyperbolic increases of both t1/2 and volume of distribution and parallel decrease of elimination rate coefficient. An elimination transport system was suggested with saturation at serum relaxin concentration of 45 ng/ml. Adverse events included local infusion site rash and pain, minor bleeding episodes, and decreased hemoglobin concentration (mean reduction 1.1 g/dl). Standard measures of scleroderma were unchanged, although global assessment favored relaxin over placebo.

CONCLUSION:

Recombinant human relaxin in the doses used was safe and well tolerated. Longer term controlled trials are warranted to define the potential efficacy of relaxin in patients with diffuse scleroderma.

• Authors: J R Seibold, P J Clements, D E Furst, M D Mayes, D A McCloskey, L W Moreland, B White, F M Wigley, S Rocco, M Erikson, J F Hannigan, M E Sanders, E P Amento
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 25 Issue 2 Pg. 302-7 (Feb 1998) ISSN: 0315-162X [Print] Canada
• PMID: 9489823 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Controlled Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Relaxin

Topics

• Adult
• Amino Acid Sequence
• Double-Blind Method
• Female
• Hemoglobinometry
• Humans
• Male
• Middle Aged
• Molecular Sequence Data
• Recombinant Proteins (administration & dosage, adverse effects, pharmacokinetics)
• Relaxin (adverse effects, genetics, pharmacokinetics)
• Scleroderma, Systemic (drug therapy)
• Treatment Outcome