[Pharmaceutical validation and error detection in the prescription of antineoplastics in oncohematological patients]. / Validación farmacéutica y detección de errores de prescripción de antineoplásicos en pacientes oncohematológicos.

OBJECTIVE: To identify the different types of cytostatic prescription errors in adult and paediatric oncohematological patients in our hospital and to propose strategies for improvement. METHODS: Longitudinal, prospective, observational study in which prescriptions for antineoplastics from the haematology and paediatric oncohaematology departments were validated over a 15-month period. The types of error were classified in accordance with the terminology and taxonomy published by Otero and cols in the document "Medication errors: standardisation of terminology and classification". Eleven variables were recorded. Amongst other parameters, the following were determined: percentage of overall error, percentage of error in type of prescription, percentage of service error, percentage of pharmaceutical intervention and level of acceptance. RESULTS: A total of 92 errors were recorded which corresponded to 1.4% of the total prescriptions. The most significant errors were: incorrect dose (28.2%), incorrect duration (21.7%), incorrect volume and/or inadequate vehicle (16.3%), and in one case a prescription was made up where the patient was allergic to the specific cytostatic drug prescribed. 81.8% of prescription errors were made manually. In the haematology department a 0.9% error was recorded, as was a 3.5% error in paediatric oncohaematology. Both the rate of pharmaceutical intervention and its level of acceptance were 100%.

[Tacrolimus blood levels and incidence of graft rejection in heart transplantation]. / Relación entre los niveles de tacrolimus en sangre y la incidencia de rechazo en enfermos trasplantados de corazón.

OBJECTIVE: To determine the relationship between pharmacokinetic parameters and clinical outcomes after heart transplantation and to determine the range of tacrolimus blood levels which provides the most effective protection against graft rejection. To study other factors that predict graft rejection. METHOD: We retrospectively analyzed the clinical outcomes of all adult patients who received a heart transplant between January 2000 and October 2003 and had routine monitoring of tacrolimus trough levels at the time of scheduled endomyocardial biopsy. Rejection was defined as Grade = 3, based on the International Society for Heart and Lung Transplantation (ISHLT) criteria. The follow-up period was 1 year. All patients were on a triple therapy regimen of Tacrolimus (TAC), Corticosteroids and Azatioprine/Micophenolate Mofetil. Data were analyzed by Student s t-test, univariate logistic regression and ROC curve. RESULTS: Tacrolimus blood levels measured at day +5 postransplant were the strongest predictor of acute graft rejection over a 1-year follow-up period (rejection 5.76 +/- 3.4 ng/ml vs no rejection 9.66 +/- 2.73 ng/ml, p = 0.016). A decrease of one unit in TAC trough level values at day +5 postransplant implied a 1.58 greater risk of rejection (p = 0.05). Overall incidence of treated acute rejection was lower for patients with trough levels higher than 8 ng/ml on day +5 postransplant (33 vs 80%, p = 0.055, Fisher s exact test). CONCLUSIONS: Data suggest that in heart transplant patients it may be crucial to achieve tacrolimus levels of at least 8 ng/ml during the first days postsurgery to avoid rejection.

New strategies of cyclosporine monitoring in heart transplantation: initial results.

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 AUC(0-4) 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 AUC(0-4). 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 adjusted 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 AUC(0-4) (r2=0.43), while C2 seemed to be the most accurate single predictor of drug exposure (r2=0.92 for AUC(0-12); r2=0.74 for AUC(0-4)). For both AUC(0-4) and AUC(0-12), 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 AUC(0-4) 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.

Clinical pharmacokinetics of tacrolimus in heart transplantation: new strategies of monitoring.

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(AUC(0-12)) was calculated by the trapezoidal rule. Using 0-4 hours TAC blood concentrations, a projected 12 hours AUC (extrapolated AUC(0-4)) 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 AUC(0-12) 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 AUC(0-4) (r2=0.98), as a good approach to patients with a poor response to treatment.