Table 3.
Alignment of drug attributes with initial desired dashboard functionality for methotrexate and tacrolimus prototypes developed at CHOP
| Drug characteristics | Dashboard functionality | |
|---|---|---|
| Methotrexate | • Anti-folate chemotherapeutic agent | • Views and predictions of: |
| • Renal excretion; enterohepatic recirculation | – MTX concentrations, creatinine clearance | |
| • Toxicity at high or prolonged low exposure | – Time to reach threshold plasma concentration | |
| • Therapeutic failure at prolonged low exposure | • Guidance for dose titration | |
| • Highly variable PK | • Diagnosis of delayed MTX clearance due to acute nephrotoxicity | |
| • Patients receive MTX based on one of several CHOP / COG protocols | • Rescue therapy guidance | |
| • TDM guided adjustment | ||
| Tacrolimus | • Inhibits IL-2-dependant T cell activation; multiple transplant settings | • Provide predictions of: |
| • Variable PK | – TAC concentrations | |
| • Wide range of oral doses (1–44 mg day−1) to maintain trough levels of 5–20 μg l−1 | – Liver function | |
| • Toxicities related to exposure include nephro and neurotoxicity, infection and lymphoproliferative disease with over-immunosuppression | – Adjustments to maintain threshold plasma concentration | |
| • TDM: 12 h trough concentration | • Guidance for dose titration | |
| • Avoid toxicities at high levels; prevent rejection at low levels: | ||
| – 45% toxicity incidence > 15 μg l−1 | ||
| – 30% incidence of acute rejection < 5 μg l−1 |