Drug (US brand name) | Oral bioavailability | Effect of food on absorption | Metabolism and clearance* | Enzyme/transporter inhibition* | Half-life in hours (range) |
Antimetabolites | |||||
Mycophenolate mofetil (MMF, CellCept) | 80.7% (renal transplant patients) 94% (healthy volunteers) |
| Rapidly hydrolyzed to its active metabolite mycophenolic acid (MPA), which is further metabolized by UGT to the inactive metabolite mycophenolic acid glucuronide (MPAG), which is excreted primarily via urine; MPA undergoes enterohepatic recirculation, and secondary increases in MPA levels are seen 6 to 12 hours after a dose of MMF | None known | 17.9 (11.4 to 24.4)¶ (MPA) MPAG can accumulate in renal failure |
Mycophenolate sodium, enteric coated (Myfortic)Δ | 72% (renal transplant patients) |
| Rapidly hydrolyzed to the active metabolite mycophenolic acid (MPA), which is further metabolized by UGT to the inactive metabolite mycophenolic acid glucuronide (MPAG), which is excreted primarily via urine; MPA undergoes enterohepatic recirculation, and secondary increases in MPA levels are seen 6 to 8 hours after a dose of mycophenolate sodium | None known | 12 (8 to 16) (MPA) MPAG can accumulate in renal failure |
Calcineurin inhibitors | |||||
Cyclosporine non-modified (Sandimmune) | Generally poor and unpredictable:
|
| Metabolized by CYP3A4 to reduced activity and inactive metabolites (eg, M1, M9, M4N) cleared fecally via bile Substrate of P-gp | Inhibitor of P-gp | 19 (10 to 27) Prolonged in hepatic impairment |
Cyclosporine modified (microemulsion) (Neoral) | 23 to 50% better absorbed than non-modified formulation in renal and liver transplant patients, respectively |
| 8.4 (5 to 18) Prolonged in hepatic impairment | ||
Tacrolimus immediate-release capsule (Prograf) | 7 to 32% |
| Metabolized by CYP3A4/5 to active (eg, 13-O-demethyl) and inactive metabolites cleared fecally via bile Substrate of P-gp | May be an inhibitor of P-gp; supportive data are limited to in-vitro effects (ie, clinical effect is unknown) | 12 (2 to 36) Prolonged in severe hepatic impairment |
Tacrolimus extended-release capsule (Astagraf XL) | 12 to 19% |
| 38 (35 to 41) Prolonged in severe hepatic impairment | ||
Tacrolimus extended-release tablet (Envarsus XR) | 50% better absorbed than immediate-release capsule |
| 31 (23 to 39) Prolonged in severe hepatic impairment | ||
mTOR inhibitors | |||||
Everolimus (Zortress) | 30% |
| Metabolized by CYP3A4 to six weakly active metabolites that are excreted primarily via feces Substrate of P-gp | None known | 30 (19 to 41) Prolonged in hepatic impairment |
Sirolimus (Rapamune) | 18% (tablet) 14% (oral solution) |
| Metabolized by CYP3A4 to seven metabolites (some have weak activity) that are excreted primarily via feces Substrate of P-gp | None known | 62 (46 to 78) Prolonged in hepatic impairment |