Search

The aim of this study was to evaluate cyclosporine (CyA) absorption profiles in heart transplantation to establish the most adequate monitoring strategy and determine the optimal therapeutic range for AUC0–4 or C2 levels. A total of 22 full pharmacokinetic studies were performed at steady-state in 22 adult heart transplant recipients (18 men, 4 women). Twelve studies were performed during the first month posttransplant (group I), and 10 studies were done after 1 month (group II). In 9 outpatients we performed an abbreviated AUC0–4. The mean age of the patients was 49 ± 15 years (range, 15–72 years), and the mean weight was 70.4 ± 10.8 kg (mean, 54–98 kg). The CyA dosage had been adjusteded to maintain trough levels (C0) in the putative target ranges of 200 to 400 ng/mL in group I and between 100 to 300 ng/mL in group II. Blood samples were drawn prior to and at 0.5, 1, 2, 4, 6, 8, and 12 hours after the morning dose. The CyA blood levels were measured by the AxSYM cyclosporine assay. The AUC was calculated by the trapezoidal rule. Multiple linear regression was done to evaluate the predictive ability of various limited sampling strategies. The C0 correlated poorly, either with the full AUC (r2 = 0.64) or the AUC0–4 (r2 = 0.43), while C2 seemed to be the most accurate single predictor of drug exposure (r2 = 0.92 for AUC0–12; r2 = 0.74 for AUC0–4). For both AUC0–4 and AUC0–12, all 2- or 3-point strategies had r2 values approaching that of the C2 value. In conclusion, C2 is a simple, fast, and accurate value to predict AUC0–4 in routine clinical practice. Its implementation must focus on ensuring the commitment of all unit staff, thus ensuring that patients are sampled on time and minimizing the impact on workload.

The aim of this study was to investigate the absorption profile of tacrolimus (TAC) in heart transplant patients in order to find the best sampling time to predict the total exposure and to explore the target range for optimal clinical immunosuppression. Twenty-five full pharmacokinetic studies were performed in 22 heart transplant patients (11 men and 7 women) at less than 1 year posttransplant. The immunosuppressive treatment was steroids plus azathioprine or mycophenolate mofetil and TAC. The mean age was 55 years (36–64 years) and the mean weight 70.49 kg (50–111 kg). After three days of receiving the same dose, eight blood samples were collected at 0.5, 1, 2, 4, 6, 8, and 12 hours postmorning dose. TAC concentrations were measured by microparticle enzyme immunoassay (IMx). Area under the concentration-time curve(AUC0–12) was calculated by the trapezoidal rule. Using 0–4 hours TAC blood concentrations, a projected 12 hours AUC (extrapolated AUC0–4) was calculated assuming C0 and C12 were comparable. A high interpatient TAC pharmacokinetics variability that was greater during the absorption phase was observed. A Cmax (30.5 ± 13.8 ng/mL) was reached at 2.3 ± 1.5 h. When target trough levels were achieved (10–20 ng/mL), the mean tacrolimus exposure was 230.6 ± 59.2 ng h/mL (120.14–327.7) (n = 19). Correlation between AUC0–12 and C0 was relatively good (r2 = 0.74). Between individual time points, C4 showed the best correlation (r2 = 0.88). In any case the best strategy to monitor is to obtain the extrapolated AUC0–4 (r2 = 0.98), as a good approach to patients with a poor response to treatment.

Combined kidney-liver transplantation is currently the best therapeutic option for patients with end-stage kidney and liver disease. We present our experience of kidney-liver transplantation in a series of 13 patients. The most frequent indications were familial amyloidotic polyneuropathy (FAP) and polycystosis of the liver and kidney. The 1- and 5-year survival rates of the liver grafts were 75% and 67%, respectively, with no kidney losses during follow-up.