Pharmacokinetics and concentration-effect relationship of adalimumab in rheumatoid arthritis
- Resource Type
- Authors
- David, Ternant; Emilie, Ducourau; Piéra, Fuzibet; Céline, Vignault; Hervé, Watier; Thierry, Lequerré; Xavier, Le Loët; Olivier, Vittecoq; Philippe, Goupille; Denis, Mulleman; Gilles, Paintaud
- Source
- British journal of clinical pharmacology. 79(2)
- Subject
- Adult
Male
Time Factors
Dose-Response Relationship, Drug
Injections, Subcutaneous
Pharmacokinetic Dynamic Relationships
Adalimumab
Middle Aged
Antibodies, Monoclonal, Humanized
Models, Biological
Arthritis, Rheumatoid
Young Adult
C-Reactive Protein
Antirheumatic Agents
Humans
Computer Simulation
Female
Tissue Distribution
Prospective Studies
Aged
- Language
- ISSN
- 1365-2125
This study aimed at describing adalimumab pharmacokinetics (PK) and the concentration-effect relationship of adalimumab using pharmacokinetic-pharmacodynamic (PK-PD) modelling in patients with rheumatoid arthritis (RA).Adalimumab PK and PK-PD data were obtained from a multicentric observational study. Adalimumab (40 mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one-compartment model. The relationship between adalimumab concentration and C-reactive protein (CRP) concentration was described using an indirect response model with inhibition of CRP input, whereas the relationship between adalimumab concentration and disease activity score in 28 joints (DAS28) was described using a direct inhibition model. Dose regimens that included a loading dose of adalimumab were simulated.Thirty patients treated for RA were analysed. The following pharmacokinetic and PK-PD parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd /F) = 10.8 l (92%); apparent clearance (CL/F) = 0.32 l day(-1) (17%); first-order absorption rate (ka ) = 0.28 day(-1) ; CRP input (kin ) = 22.0 mg l(-1) day(-1) (65%); adalimumab concentration leading to a 50% decrease in kin (C50 ) = 3.6 mg l(-1) (88%); baseline DAS28 (DAS0 ) = 5.5 mg l(-1) (11%); and adalimumab concentration leading to 50% decrease of DAS0 (IC50 ) = 11.0 mg l(-1) (71%). Simulations showed that a 160 mg loading dose should reduce the time to reach efficacy in terms of both CRP and DAS28 after the first injection.This is the first study to describe adalimumab pharmacokinetics and the concentration-effect relationship in RA. A 160 mg loading dose may lead to an increased benefit from treatment in RA patients.