Premium
Disease–Drug–Drug Interaction Involving Tocilizumab and Simvastatin in Patients With Rheumatoid Arthritis
Author(s) -
Schmitt C,
Kuhn B,
Zhang X,
Kivitz AJ,
Grange S
Publication year - 2011
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2011.35
Subject(s) - tocilizumab , medicine , rheumatoid arthritis , simvastatin , bioequivalence , confidence interval , pharmacokinetics , meloxicam , pharmacology , gastroenterology
In rheumatoid arthritis (RA), interleukin‐6 (IL‐6) concentration is elevated, which may cause reduced cytochrome P450 (CYP) activity and increased exposure (peak plasma concentration and area under the plasma concentration‐vs.‐time curve (AUC)) to certain drugs. Tocilizumab may reverse IL‐6‐induced suppression of CYP3A4 activity. In this study, exposure to simvastatin was significantly reduced at 1 and 5 weeks after tocilizumab infusion in 12 patients with RA. The mean effect ratio for simvastatin AUC last was 43% (90% confidence interval (CI), 34–55%) at 1 week after tocilizumab infusion (day 15) and 61% (90% CI, 47–78%) at 5 weeks after tocilizumab infusion, as compared with baseline (day 1); both ratios were significantly lower than the bioequivalence boundary (80–125%). Mean plasma C‐reactive protein (CRP) levels normalized within 1 week after tocilizumab was initiated; the time course of tocilizumab's CRP‐reducing effect paralleled that of simvastatin pharmacokinetics. The study findings suggest that caution should be exercised when starting tocilizumab in RA patients who are taking simvastatin. Clinical Pharmacology & Therapeutics (2011) 89 5, 735–740. doi: 10.1038/clpt.2011.35