Larger dosage required for everolimus than sirolimus to maintain same blood concentration in two pancreatic islet transplant patients with tacrolimus.
We attempted a switch of mammalian target of rapamycin (mTOR) inhibitors from sirolimus to everolimus, a derivative of sirolimus and now on the market in Japan, in two pancreatic islet transplant patients. Both patients were administered tacrolimus with sirolimus or everolimus. They had been administered 5 or 9 mg sirolimus once a day and had maintained a trough concentration of about 15 ng/mL as measured by high performance liquid chromatography with ultraviolet detection. After the switch from sirolimus to everolimus, they were given 10 or 12 mg/day of everolimus twice a day to maintain a trough concentration of 12-15 ng/mL as measured by a fluorescence polarization immunoassay (FPIA) method. Afterward, the blood concentrations of everolimus and sirolimus after the conversion were measured by high performance liquid chromatography with mass spectrometry and everolimus concentrations were found to be 5-10 ng/mL. These data show that a larger dosage is needed for everolimus than sirolimus to maintain the same trough blood concentration. Data obtained by the FPIA for everolimus should be carefully evaluated after switching from sirolimus to everolimus because of the cross-reactivity of the antibody with sirolimus.
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Eriko
E
Sato
Ikuko
I
Yano
Masahiro
M
Shimomura
Satohiro
S
Masuda
Toshiya
T
Katsura
Shin-ichi
S
Matsumoto
Teru
T
Okitsu
Yasuhiro
Y
Iwanaga
Shinji
S
Uemoto
Ken-Ichi
K
Inui
D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring; D000068338:Everolimus; D005260:Female; D016231:Fluorescence Polarization Immunoassay / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents; D007515:Islets of Langerhans; D016381:Islets of Langerhans Transplantation; D016030:Kidney Transplantation; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood*; D016559:Tacrolimus / Q000097:blood*; D014018:Tissue Distribution
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus