Table 3.
Half‐life elimination of IBD medications
| Drug | Half‐life and time to reach therapeutic effect | Elimination half‐life (Most drugs considered to have negligible effect after four‐to‐five half‐lives) |
How long the immunosuppression lasts 50% drug eliminated after one elimination half‐lives 75% drug eliminated after two elimination half‐lives 99% drug eliminated after seven elimination half‐lives |
|---|---|---|---|
| Thiopurines (Azathioprine and mercaptopurine) |
t 1/2:6‐TGN and 6‐MMP in RBC = 5 days 124 Steady state: 6‐TGN and 6‐MMP = 4 weeks in RBC 124 Median time to clinical response: 4.5 months 125 |
6‐TGN in RBC: 6.8 days [IQR 5.9‐8.4 days] 126 , a |
75% of 6‐TGN eliminated after 10‐14 days and expected to be negligible by day 40. 126 Immune reconstitution occurs quickly after thiopurine cessation, if the antigen was not encountered whilst on the thiopurine therapy. 126 |
| Adalimumab | The subcutaneous injection has a bioavailability of 64% and peak drug concentration at day 5 following injection 127 |
17.8‐23.9 days (in RA population) 128 Clearance of 0.33L/day 13 |
75% eliminated after approximately 40 days |
| Infliximab | IV infusion 8‐9.5 days | 7‐12 days 129 , 130 |
75% eliminated after 2‐3 weeks Low volume of distribution (3‐6L/kg) and very low systemic clearance of 11‐15ml/hr, mean infliximab is predominantly in the intravascular space for 12‐17 days prior to elimination 129 , 130 Low albumin and higher body weight will speed up elimination 131 |
| Tofacitinib | 3‐3.8 hours | 3 hours |
After a single dose, 95% is expected to be eliminated within 24 hours. Pharmacodynamic effects generally reversible in 14 days after discontinuation |
| Methotrexate | Methotrexate in serum has a half‐life of 6 hours but is converted quickly to methotrexate polyglutamate which is stored for much longer in liver and erythrocytes. 132 | 3‐10 hours (for methotrexate, not activity) | 75% of methotrexate eliminated by within 24 hours but effect continues through active metabolites. |
| Ustekinumab | First dose given IV to reach peak concentration | 19 days |
Eliminated at 0.19 L/day (IBD) 75% eliminated by 38 days |
| Golimumab | 2‐2.3 days (RA Populations) 128 | 14 days |
Clearance 7.6 mL/kg/kg 75% eliminated by approx. 30 days |
| Vedolizumab | Although given intravenously, clinical effect can takes weeks | 25 days |
Cleared at 0.157 L/day 75% eliminated by 50 days |
Low numbers, n = 9 with missing data. 126