Table 2.
Population PK models, PK parameters and covariates for JAK inhibitors currently used or developed for the treatment of inflammatory bowel diseases.
| Drug | PK model | Population PK parameters | Dosing regimen | ||
|---|---|---|---|---|---|
| Parameters | Covariates | ||||
| Tofacitinib | One-compartment model with first order absorption and elimination in adult patients with UC26 | CL/F [L/h] %CV [CL/F] V/F [L] Ka [/h] %CV [Ka] Tlag [h] | 22.4 31.4 94.2 2.83 87.5 0.16 | No covariates were identified to have an effect on tofacitinib exposure | Patients with UC administered with placebo or oral tofacitinib doses of 0.5, 3, 10, 15 mg BID for 8 weeks26 |
| Filgotinib | Three-compartment model with first-order oral absorption and elimination in healthy subjects27 | CLp/F [L/h] %CV [CLp/F] Vc/F [L] %CV [Vc/F] Q/F [L/h] Vp/F [L] CLM/F [L/h] %CV [CLM/F] VM/F [L] %CV [VM/F] Ka [/h] | 3.97 8.0 3.08 52 2.002 4.72 1.004 20.3 4.36 4.7 -0.733 | Decreased CLp/F with body weight and sex was found to affect Vc/F [L] | Healthy male subjects administered either placebo or oral filgotinib single doses ranging from 10 mg to 200 mg and, subsequently, multiple doses of 25, 50, 100 mg BID or 200, 300, 450 mg QD for 10 days27 |
| Upadacitinib | Two-compartment model with first-order absorption and elimination in healthy subjects28 | CL/F [L/h] %CV [CL/F] Vc/F [L] %CV [Vc/F] Ka [1/h] %CV [Ka] Tlag [h] Vp/F [L] Q/F [L/h] | 39.7 16 146 14 12.3 150 0.48 64.3 3.23 | CL/F and Vc/F was decreased in females compared with males, CL/F was decreased with increased creatine clearance, Vc/F was decreased with increased body weight | Healthy subjects administered placebo or upadacitinib single doses of 1, 3, 6, 12, 24, 36 or 48 mg, or multiple doses of 3, 6, 12, and 24 mg BID for 14 days29 |
PK, pharmacokinetics; BID, twice daily; QD, once daily; CL/F, oral clearance; CLp/F, oral clearance for the parent compound; CLM/F, oral clearance for the metabolite compound; CV, coefficient of variation; Ka, absorption rate constant; Q/F, oral intercompartmental clearance; T1/2, half-life; UC, ulcerative colitis; V/F, oral volume of distribution; Vc/F, oral volume of distribution for the central compartment; Vp/F, oral volume of distribution for the peripheral compartment; VM/F, oral volume of distribution for the metabolite compound; Tlag, absorption lag time.