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C2 Monitoring (c2 + monitoring)
Selected AbstractsA randomized, prospective, pharmacoeconomic trial of neoral 2-hour postdose concentration monitoring versus tacrolimus trough concentration monitoring in de novo liver transplant recipientsLIVER TRANSPLANTATION, Issue 2 2008Surendra Shenoy Two-hour postdose cyclosporine (C2) monitoring is becoming an accepted method of therapeutic drug monitoring, although it is not known whether C2 monitoring is superior to tacrolimus (FK)-based immunosuppression. The purpose of this trial was to compare the safety, efficacy, and pharmacoeconomics of cyclosporine A (CsA) monitored by C2 levels versus FK monitored by trough levels in de novo liver transplant recipients. After informed consent, 60 de novo liver transplant recipients were randomized in a 1:1 fashion to receive either FK (trough, 6-10 ng/mL) or CsA (C2, 600-1200 ng/mL) and corticosteroids. The 2 groups were similar for gender, race, indication for liver disease, and age. At 1 year, patient survival was similar (93% for FK versus 90% for C2). One patient in the FK arm was retransplanted because of recurrent hepatitis C virus (HCV). Early acute rejection occurred in 27% of FK-treated patients and 23% of CsA-treated recipients [P = not significant (NS)]. Recurrent HCV occurred in 21% of FK-treated patients and 61% of CsA-treated patient (P = 0.04). The incidence of other infections, new onset diabetes mellitus, requirement for antihypertensives, and requirement for cholesterol medications were similar between the groups. Annual calcineurin inhibitor costs were lower in the C2 arm ($5432 ± 2091 for C2 versus $8291 ± 3948 for FK, P = 0.001). Annual pretransplant drug costs ($2292 ± 2331 for C2 versus $2831 ± 2358 for FK, P = NS) and 1-year posttransplant drug costs ($17,214 ± 16,600 for C2 versus $15,151 ± 11,699 for FK, P = NS) were similar. In conclusion, immunosuppression with CsA, monitored by C2 levels, is safe, effective, and economical in liver transplant recipients and provides immunosuppression at least equivalent to that of FK. Liver Transpl 14:173,180, 2008. © 2008 AASLD. [source] 12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus,,LIVER TRANSPLANTATION, Issue 10 2006Gary Levy The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C,positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 ± 50 days) than with tacrolimus (70 ± 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 ,mol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline. Liver Transpl 12:1464,1472, 2006. © 2006 AASLD. [source] How common is delayed cyclosporine absorption following liver transplantation?LIVER TRANSPLANTATION, Issue 2 2005Silvina E. Yantorno The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA ,10 mg/kg/day (C2 monitoring) and in 15 maintenance patients. Patients were categorized as ,normal' absorbers (C2 exceeding C4 and C6) or ,delayed' absorbers (C4 or C6 exceeding C2), and as ,good' (>800 ng/mL at C0, C2, C4, or C6) or ,poor' absorbers (C0, C2, C4 and C6 <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had ,normal' CsA absorption and 12 (44%) ,delayed' absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6 / 15, 40%) or delayed (5 / 12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C4. Mean C0 level was significantly higher in delayed absorbers (282 ± 96 ng/mL) than in normal absorbers (185 ± 88ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C2 > C4) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C4 in addition to C2 differentiates effectively between delayed and poor absorbers of CsA such that over- or underimmunosuppression can be avoided. (Liver Transpl 2005;11:167,173.) [source] C2 monitoring of cyclosporine in de novo liver transplant recipients: The clinician's perspectiveLIVER TRANSPLANTATION, Issue 5 2004Federico Villamil Adjusting cyclosporine (CsA) dose based on blood concentration at 2 hours after dose (C2) has been shown in prospective clinical trials to reduce the risk of rejection compared with conventional trough monitoring. In addition, it provides equivalent efficacy to tacrolimus in liver transplant patients, with a favorable safety profile. Target C2 should be defined on an individual basis depending on adjunctive therapy and the level of exposure required. It appears less critical to achieve target C2 in the first few days after liver transplantation than was previously believed. Achieving target C2 exposure in the initial period after transplant requires that changes in the proportion of cyclosporine absorbed from the gut be taken into account to avoid risk of overexposure. In addition, if a starting dose of 10,15 mg/day is used, it is advisable to delay increasing the dose until a trend in C2 level indicates this to be necessary. Immediate dose reduction is required if C2 exceeds target range. In patients with low C2 values, cyclosporine concentration at a later time point should be measured to establish whether the patient is a poor absorber or a delayed absorber of C2, and dose adjustments should be undertaken accordingly. In conclusion, this more flexible approach to C2 monitoring allows the dose of cyclosporine to be individualized effectively for each patient, which results in significant efficacy benefits while minimizing the risk of toxicity. (Liver Transpl 2004;10:577,583.) [source] Impact of cyclosporine 2-h level and mycophenolate mofetil dose on clinical outcomes in de novo heart transplant patients receiving anti-thymocyte globulin inductionCLINICAL TRANSPLANTATION, Issue 2 2003Marcelo Cantarovich Abstract: Background: Cyclosporine (CsA) 2-h post-dose level (C2) correlates better than trough levels (C0) with the area under the curve. We evaluated the clinical impact of C2 and mycophenolate mofetil (MMF) dose in adult heart transplant patients receiving anti-thymocyte globulin (ATG) induction. Methods: Two immunosuppressive strategies were sequentially evaluated. In Group 1 (13 patients), simultaneous C0/C2 (ng/mL) were analyzed. CsA dose monitoring was initially based on C0 : <3 months: 200,300, 4,6 months: 150,250, 6,9 months: 100,200, and on C2 thereafter (as in Group 2). In Group 2 (nine patients), C2 monitoring was implemented: <3 months: 600,800, 4,6 months: 500,700, >6 months: 400,600. All patients received ATG induction, corticosteroids, and MMF (1.0 g b.i.d. in Group 1 and 1.5 g b.i.d. in Group 2). Results: Patients in Group 2 received higher MMF doses during the first trimester. C2 at 1, 3, 6, 12, 24, and 36 months was, respectively, 1199 ± 476, 1202 ± 587, 999 ± 467, 664 ± 203, 593 ± 208, and 561 ± 147 in Group 1, and 809 ± 160 (p = 0.02), 644 ± 178 (p = 0.003), 664 ± 169 (p = 0.02), 616 ± 221, 464 ± 234, and 451 ± 165 in Group 2. The incidence of acute rejection (grade ,3A) at 6, 12, 24, and 36 months was, respectively, 38.5, 38.5, 46, and 54% in Group 1, and 11, 44, 56, and 56% in Group 2 (p = NS). At 3 months, the creatinine clearance was 25% lower in Group 1. Thereafter, renal function remained stable in both groups. Conclusion: Our results suggest that heart transplant patients receiving ATG induction may experience similar outcomes with either a higher C2 and a lower MMF dose or a lower C2 and a higher MMF dose. These results could be considered to design prospective studies to optimize C2 monitoring, to reduce the incidence of acute rejection without increasing the risk of renal dysfunction. [source] | ||||||||||