Mepolizumab is a fully humanized monoclonal antibody (IgG1/k) targeting @entity1 @entity225 ( @entity225 ), a key haematopoietin needed for eosinophil development and function. Mepolizumab blocks @entity1 @entity225 from binding to the a-chain of the @entity225 receptor complex on the eosinophil cell surface, thereby inhibiting @entity225 signalling. The pharmacokinetics of mepolizumab have been evaluated in clinical studies at doses of 0.05-10   mg/kg and at 250   mg, 750   mg and 1500   mg. Mepolizumab was eliminated slowly, with mean initial and terminal phase half-life values of approximately 2 and 20 days, respectively. Plasma clearance ranged from 0.064 to 0.163   mL/h/kg and steady-state volume of distribution ranged from 49 to 93   mL/kg. Pharmacokinetics were dose proportional and time independent. Estimates based on a two-compartment intravenous infusion model from @entity1 with @entity565 or healthy subjects following single doses predicted mepolizumab plasma concentrations in multiple-dose studies involving @entity1 with @entity5441 ( @entity5441 ), @entity565 or @entity1712 . The absolute bioavailability of mepolizumab was 64-75% following subcutaneous injection and 81% following intramuscular injection. Peripheral blood eosinophil levels decreased in healthy subjects and @entity1 with @entity5441 , @entity565 , @entity1712 or @entity483 after intravenous mepolizumab infusion and subcutaneous injection. Reductions in eosinophil counts in oesophagus, sputum, skin, bone marrow, nasal lavage fluid and/or bronchial mucosa after treatment with mepolizumab were observed in placebo-controlled studies in various indications. The relationship between percentage change from baseline in blood eosinophils and mepolizumab plasma concentrations was described by an indirect pharmacological response model. The estimated maximal decrease in eosinophil count was approximately 85% from baseline and the half-maximal inhibitory concentration (IC50) was approximately 0.45    g/mL.

Pharmacokinetics and pharmacodynamics of mepolizumab, an anti- XXXX monoclonal antibody.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity1712 :: ('MESH:D004802', 'Disease') :: ['eosinophilic oesophagitis'] @entity483 :: ('MESH:D003876', 'Disease') :: ['atopic dermatitis'] @entity225 :: ('3567', 'Gene') :: ['interleukin-5', 'IL-5'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity5441 :: ('MESH:D017681', 'Disease') :: ['hypereosinophilic syndrome', 'HES']
@entity225 :: (3567,Gene) :: ['interleukin-5']
