Biomedical subjects

Hiroyuki Furukawa

Publications and source records attributed to Hiroyuki Furukawa.

40 records · Page 3Linked to original sources

PubMed2002

A novel leflunomide derivative, FK778, for immunosuppression after kidney transplantation in dogs.

BACKGROUND: Leflunomide and its metabolite, A77 1726, interfere with pyrimidine metabolism and exert potent immunosuppression in experimental organ transplantation. However, clinical use of the agents has been restrained because of an extended half-life. FK778, one synthetic malononitrilamide derived from A77 1726, is synthesized to overcome this problem while maintaining similar therapeutic efficacy. METHODS: Immunosuppressive effect, pharmacokinetics, and adverse events of FK778, as a single drug treatment or combination with tacrolimus or cyclosporine, were determined in a canine kidney transplantation model. The agents were daily administered orally to the animals for 90 days after surgery. Animal survival, pharmacokinetics, biochemistry, hematology, and histopathology were evaluated. RESULTS: FK778 at 4 mg/kg prolonged median survival of the control animals from 10 days to 30.5 days. Administration of 4 mg/kg FK778 with 0.3 mg/kg tacrolimus or 10 mg/kg cyclosporine increased median survival to 75.5 days and 50.5 days, respectively. In combined treatments, trough levels of FK778 at 4 mg/kg ranged between 40 microg/mL and 100 microg/mL after 1 month. Vomiting and diarrhea were common in animals given FK778. Bone marrow suppression was seen at higher doses. CONCLUSIONS: FK778 is a promising new immunosuppressant that may be used in combination with current standard drugs in organ transplantation.

Alkynes↗

PubMed2002

[Liver transplantation for patients with hepatitis B/C virus cirrhosis or hepato cellular carcinoma].

The outcome of liver transplantation for patients with hepatitis B/C virus (HBV/HBC) cirrhosis or with hepatocellular carcinoma(HCC) was deemed pessimistic until the early 1990s due to the high rate of recurrence and mortality. However, with the advent of new antiviral agents and strict adherence transplant indications, the results of liver transplantation in patients with these disease have improved progressively. Coadministration of lamivudine and anti-HBV immunoglobulin, and of interferon and ribavirin inhibits the recurrence of hepatitis B and hepatitis C, respectively. Excluding HCC patients with extrahepatic or lymph node metastasis, vascular invasion, a single lesion more than 5 cm in diameter, or multiple lesions more than 3 cm in diameter, the 5-year patient survival rate has improved from 30% to 85%, with a disease-free survival rate of more than 90%. However, the development of lamivudineresistant mutants after prolonged use of the agent needs to be overcome, possibly by new antiviral agents such as adefovir. In addition, to expand the current limited transplant indications for HCC, the efficacy of perioperative anticancer treatment and the importance of molecular diagnosis of circulating hepatoma cells must be determined in future.

Adult↗

PubMedDate not supplied

A nomogram for predicting the optimal oral dosage of tacrolimus in liver transplant recipients with small-for-size grafts.

No optimal tacrolimus dosage regimen suitable for clinical use in liver transplant recipients has yet been established. The purpose of this study was to determine the factors affecting the optimal dosage and pharmacokinetics of tacrolimus in living donor liver transplantation, and a nomogram for optimal tacrolimus dosage in the immediate postoperative period for recipients with small-for-size grafts was constructed. Twenty-four liver transplant patients (nine males and 15 females) and 24 donors (10 males and 14 females) were enrolled in this study. Two studies were performed. In study 1, the effect of the actual ratio of graft volume to standard liver volume (GV/SV ratio) on the elimination half-life (T1/2) of tacrolimus in the immediate postoperative period was analysed, and a nomogram for estimating the optimal oral dose of tacrolimus required to reach a target concentration was established. In study 2, the effect of donor age on the recovery of hepatic function with ability of the graft to eliminate tacrolimus was analysed. In the immediate postoperative period, T1/2 of tacrolimus showed great variability between patients, with values ranging from 16.3 to 110.9 h. Graft size (GV/SV ratio) is important and could influence intraindividual variations in the optimal dosage and T1/2 of tacrolimus. The recovered T1/2 ratio (T1/2 ratio=T1/2 1-10 d/T1/2 30-40 d), this ratio being related to the recovery of hepatic function with ability of the graft to eliminate tacrolimus, showed great variability between patients, with values ranging from 1.08 to 4.21 (mean+/-SD, 1.95+/-0.81). Age of the donor is a major factor affecting the recovered ratio of the graft to metabolize tacrolimus. The nomogram that we have constructed, based on graft size (GV/SV ratio), will easily provide optimal dose for each patient with small-for-size graft in the early postoperative period.

Adolescent↗

PubMedDate not supplied

Cost-utility of living donor liver transplantation in a single Japanese center.

BACKGROUND/AIMS: Living donor liver transplantation is becoming increasingly important in the Western world, but the economic issues remain controversial. We conducted a cost-utility analysis to evaluate whether living donor liver transplantation is cost-effective. METHODOLOGY: Cost and utility analyses were performed in a longitudinal survey of a single center in Sapporo, Japan. Medical costs were derived from 11 patients who underwent living donor liver transplantation. Health utility was measured in quality-adjusted life year. Data for health utility scores were derived from 19 patients who underwent living donor liver transplantation. RESULTS: Median medical cost was U.S. dollars 154,626 from the first day of preoperative evaluation to 24 months post-transplantation. Cumulative quality-adjusted life years were 1.60 at 24 months after transplantation. Medical cost per quality-adjusted life year decreased progressively, leading to medical cost of U.S. dollars 605,131 per quality-adjusted life year at 3 months to U.S. dollars 94,169 at 24 months after transplantation. The results were sensitive to medical cost. CONCLUSIONS: Follow-up survey identified progressive increases in the cost-effectiveness of living donor liver transplantation for patients with end-stage liver disease. Living donor liver transplantation appears to represent a cost-effective medical technology.

Adolescent↗