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Titolo:
Orthotopic liver transplantation using low-dose tacrolimus and sirolimus
Autore:
McAlister, VC; Peltekian, KM; Malatjalian, DA; Colohan, S; MacDonald, S; Bitter-Suermann, H; MacDonald, AS;
Indirizzi:
Dalhousie Univ, Atlantic Canada Liver Transplantat Program, Halifax, NS, Canada Dalhousie Univ Halifax NS Canada ansplantat Program, Halifax, NS, Canada
Titolo Testata:
LIVER TRANSPLANTATION
fascicolo: 8, volume: 7, anno: 2001,
pagine: 701 - 708
SICI:
1527-6465(200108)7:8<701:OLTULT>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAPAMYCIN; CYCLOSPORINE; FK506; IMMUNOSUPPRESSANT; PHARMACOKINETICS; IMMUNOASSAY; COMBINATION; EFFICACY; SURVIVAL; THERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: McAlister, VC London Hlth Sci Ctr, Univ Hosp 4TU40, London, ON N6A 5A5, Canada London Hlth Sci Ctr London ON Canada N6A 5A5 6A 5A5, Canada
Citazione:
V.C. McAlister et al., "Orthotopic liver transplantation using low-dose tacrolimus and sirolimus", LIVER TRANS, 7(8), 2001, pp. 701-708

Abstract

Although sirolimus (SRL) binds the immunophilin FK506-binding protein-12 (FKBP-12) with greater avidity than tacrolimus (TAC), animal studies have shown that SRL and TAC act synergistically to prevent rejection. Dose-relatedtoxicity is more often the cause of TAC discontinuation than rejection. Wehypothesized that SRL would allow for a substantial reduction in the concomitant dose of TAC after liver transplantation to levels less than the threshold for toxicity. A series of 56 liver transplant recipients were administered a combination of SRL and TAC (target trough levels, 7 and 5 ng/mL, respectively). Planned weaning of steroids commenced after 3 months. Pharmacokinetic (PK) studies were undertaken. Patient and graft survival were 52 patients (93%) and 51 grafts (91%), with a follow-up of 23 months (range, 6 to 35 months). One episode (1.8%) of hepatic artery thrombosis was seen. Therate of acute cellular rejection was 14%. No extra treatment was administered in 3 of 8 patients, and the other 5 episodes responded to a single course of steroids. Cytomegalovirus infection occurred in 4 patients (7%). Renal function, glucose control, and lipid metabolism are near normal in 47 patients (84%) without additional medication. Steroid elimination is completedin 51 patients (91%). Bioavailability of SRL and TAC varied between transplant recipients, but trough levels strongly correlated with the area under the curve (r(2) = 0.82 and r(2) = 0.84, respectively). Simultaneous administration did not affect the PK profile of the drugs at this dose. The ratio of trough level to daily dose correlated between SRL and TAC. The synergistic effect seen in animal models also occurs in clinical liver transplant recipients on SRL-TAC combination immunosuppression. A low-dose combination of SRL and TAC should be compared with conventional immunosuppression in a multi-center, randomized, controlled trial.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 09:15:56