Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis.
Background: Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis.Methods: This analysis characterizes the population pharmacokinetics of subcutaneous tildrakizumab and identifies covariates influencing exposure in 2098 healthy...
| Publicado en: | Clinical Pharmacokinetics Vol. 58; no. 8; pp. 1059 - 1069 |
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| Autores principales: | , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Aug2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=137398012&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137398012 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03125963 C4U jtl: Clinical Pharmacokinetics issn: 03125963 maglogo: N pubinfo: dt: Aug2019 vid: 58 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 137398012 137398012 NLM30915660 137398012 10.1007/s40262-019-00743-7 NLM30915660 137398012 ppf: 1059 ppct: 10 formats: tig: atl: Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis. aug: au: Jauslin, Petra Kulkarni, Pooja Li, Hanbin Vatakuti, Suresh Hussain, Azher Wenning, Larissa Kerbusch, Thomas affil: Certara USA, Inc., Princeton, NJ, USA sug: subj: Interleukins Antagonists and Inhibitors Antibodies, Monoclonal Psoriasis Drug Therapy Adult Body Weight Human Psoriasis Ethnology Female Middle Age Antibodies, Monoclonal Administration and Dosage Male Serum Albumin Creatinine Analysis Case Control Studies Injections, Subcutaneous Chronic Disease Biological Availability Antibodies, Monoclonal Therapeutic Use Validation Studies Comparative Studies Evaluation Research Multicenter Studies Clinical Assessment Tools Scales Adult: 19-44 years Middle Aged: 45-64 years Female Male ab: Background: Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis.Methods: This analysis characterizes the population pharmacokinetics of subcutaneous tildrakizumab and identifies covariates influencing exposure in 2098 healthy volunteers and subjects with psoriasis. Tested covariates included body weight, formulation type, sex, age, race, serum albumin, creatinine clearance, Japanese origin, prior treatment with a biologic agent, subject status (subjects with psoriasis vs. healthy volunteers), and ethnicity.Results: The pharmacokinetics was described by a one-compartment model with first-order absorption and elimination kinetics, and inter-individual variability on clearance, volume of distribution, and absorption rate constant. The pharmacokinetics was characterized by low clearance and limited volume of distribution. In subjects with psoriasis, the geometric mean clearance (coefficient of variation) was 0.32 L/day (38%), volume of distribution was 10.8 L (24%), and absorption and elimination half-life were 1.5 days (18%) and 23.4 days (23%), respectively, with an absorption lag time of 1.2 h. For the 100-mg dose, steady-state area under the plasma concentration vs. time curve for one dosing interval and maximum plasma concentration were 305 µg*day/mL (41%) and 8.1 µg/mL (34%), respectively. Steady state was achieved by 16 weeks with the clinical regimen (dosing on week 0 and week 4 and every 12 weeks thereafter) with 1.1-fold accumulation in maximum plasma concentration. Healthy subjects had 31% higher bioavailability than subjects with psoriasis. Subjects with increased body weight had a lower area under the plasma concentration-time curve at steady state vs. those with lower body weight. The modeled exposures were contained within clinical comparability bounds for all covariates including body weight.Conclusions: The pharmacokinetics of tildrakizumab behaves like a typical monoclonal antibody without requiring dosage adjustment.Trial Registration: NCT01729754, NCT01225731, NCT01722331. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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