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ABSTRACT: Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.
Pharmacotherapy 10/2008; 28(9):1188-93. · 2.90 Impact Factor
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American Journal of Health-System Pharmacy 06/2006; 63(10):949-52. · 1.96 Impact Factor
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Hee Chul Yu, Sony Tuteja,
Jang Il Moon,
Gary I Kleiner,
Lobella Conanan,
Jeffrey J Gaynor,
Tomoaki Kato,
David M Levi,
Seigo Nishida,
Gennaro Selvaggi,
Carlos Gandia,
Debbie Weppler,
Violet Esquenazi,
Phillip Ruiz,
Joshua Miller,
Andreas G Tzakis
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ABSTRACT: Citrulline concentrations have been proposed as a marker for intestinal allograft rejection. We instituted dried blood spot (DBS) specimen monitoring of citrulline to simplify sample collection posttransplant. This study demonstrates the correlation between plasma and dried blood spot specimen citrulline concentrations after intestinal transplantation.
Plasma and DBS samples were analyzed by hydrophilic interaction chromatography tandem mass spectrometry. Comparison of the strength of linear correlation was made according to the type of surgery, sonication time, DBS citrulline levels, and the time interval between the blood sample collection and the assay date.
A very strong linear correlation exists between the plasma and DBS citrulline concentrations (r=0.87; P<0.001). The correlation between plasma and DBS citrulline concentrations was maintained when evaluating only the intestinal transplant recipients. There was no significant difference in the strength of linear correlation according to sonication time, cirtrulline concentrations, or length of time to assay date.
DBS citrulline monitoring will ease sample collection following intestinal transplantation and improve the ability to detect intestinal dysfunction and rejection by a noninvasive means.
Transplantation 01/2006; 80(12):1729-33. · 4.00 Impact Factor
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Clinical Gastroenterology and Hepatology 04/2004; 2(3):183-97. · 5.63 Impact Factor
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ABSTRACT: Although it is well established that acute rejection is one of the major risk factors for chronic graft loss following kidney transplantation, its effect on long-term graft survival following simultaneous kidney-pancreas transplants (SKPTs) is less well known. We analyzed a large cohort of SKPTs and cadaver kidney transplants reported to the United Network for Organ Sharing database during 1988-97, to determine the impact of acute rejection episodes on long-term kidney and pancreas graft survival. Only patients whose kidney and pancreas grafts had survived for at least 1 year were included. Other potential risk factors influencing long-term graft survival were included in the analysis. Of the 4251 SKPTs, 45% had no acute rejection, 36% had kidney only rejection, 3% had pancreas only rejection, and 16% had both kidney and pancreas rejection within the 1st year post transplant. The 5-year kidney and pancreas graft survival rates adjusted for other risk factors were 91% and 85%, respectively; for those with no acute rejection episodes, 88% and 84%, respectively; for those with kidney only rejection, 94% and 83%, respectively; for those with pancreas only rejection; and 86% and 78%, respectively, for those with both kidney and pancreas rejection. The relative risk (RR) of kidney graft failure was 1.32 when acute rejection involved the kidney graft only, while the RR was 1.53 when the rejection involved both organs. We conclude that acute rejection episodes have a negative impact on the long-term kidney graft survival in the SKPT population similar to that in the cadaver kidney transplant population. Patients who had acute rejection episodes of both kidney and pancreas have the worst long-term graft survival.
American Journal of Transplantation 05/2003; 3(4):439-44. · 6.39 Impact Factor
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ABSTRACT: Sirolimus (SIR) in combination with cyclosporine reduces the incidence of acute rejection in renal transplant recipients. Limited data are available regarding SIR in combination with tacrolimus (TAC).
A single-center, retrospective review of renal transplant recipients receiving SIR, TAC, and corticosteroids postoperatively was conducted. A total of 118 consecutive renal transplant recipients were included on the basis of availability of day 1 SIR dose information. Seventy-seven patients received an SIR loading dose (SIR-LD) immediately posttransplantation, and 41 patients did not (SIR no loading dose [SIR-NLD]).
The two groups showed similar demographic and transplant characteristics. SIR doses and trough levels were significantly higher in the SIR-LD patients at 1 and 7 days posttransplantation; however, no differences occurred beyond day 7. Patients receiving an SIR-LD experienced significantly better freedom from rejection at 1, 3, and 6 months posttransplantation (P<0.05). This rejection benefit in the SIR-LD group was independent of donor source and use of antibody induction. SIR-LD patients experienced fewer serious infections (12% SIR-LD vs. 27% SIR-NLD, P=0.04) and a lower incidence of delayed graft function (21% SIR-LD vs. 39% SIR-NLD, P<0.05). No significant differences in serum creatinine, hemoglobin, and platelet counts occurred in the first 180 days posttransplantation, but the patients in the SIR-NLD group experienced lower hemoglobin levels at day 30 than those in the SIR-LD group (10.8 g/dL SIR-LD vs. 9.7 g/dL SIR-NLD, P=0.03).
SIR-LD significantly improves early posttransplantation freedom from rejection in renal transplant recipients without increasing other complications.
Transplantation 01/2003; 75(1):86-90. · 4.00 Impact Factor
