Prospective Randomized Trial Investigating the Influence of Pharmaceutical Care on the Intra-Individual Variability of Tacrolimus Concentrations Early After Kidney Transplant.

BACKGROUND: This study evaluated the influence of pharmaceutical care (PhC) in the intra-individual variability of dose-corrected whole blood tacrolimus (TAC) trough concentrations, adherence to immunosuppressive therapy and clinical outcomes. METHODS: We randomized 128 kidney transplant recipients to receive PhC consisted of predefined instructions provided by a pharmacist (PhC group, n = 64) or standard nurse staff instructions (control group, n = 64) from day 3 to day 90 after kidney transplantation. The study was powered to detect at least 50% reduction in the coefficient of variation (%CV), calculated from 6 dose-corrected whole blood TAC trough concentrations, in the PhC group. Patient adherence was evaluated using Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) questionnaire. RESULTS: There was no difference in the %CV comparing PhC and control group (31.4% ± 12.3% versus 32.5% ± 16.1%, P = 0.673). There were no differences in the proportion of patients showing TAC concentrations within predefined target concentrations in each study visit. There was no difference in the proportion of nonadherent patients at day 28 (17% versus 26%, P = 0.135) and day 90 (27% versus 25%, P = 0.457) based on BAASIS questionnaire answers, respectively. There were no differences in clinical outcomes. CONCLUSIONS: Universal PhC in addition to standard nurse staff instruction was not associated with reduced intra-individual variability of dose-corrected whole blood TAC trough concentrations or improved adherence.

Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens.

STUDY OBJECTIVE: To evaluate the safety and tolerability of immunosuppressive drugs used in a planned randomized conversion from a calcineurin inhibitor, tacrolimus, to a mammalian target of rapamycin inhibitor, sirolimus, in de novo kidney transplant recipients. DESIGN: Prospective safety analysis of data from a prospective, randomized, open-label, controlled study. PATIENTS: A total of 119 adult kidney transplant recipients who received tacrolimus (TAC), mycophenolate sodium (MPS), and prednisone between February 2008 and May 2010; after 3 months of this regimen, 60 of these patients were randomized to conversion from TAC to sirolimus (SRL/MPS group), and 59 patients continued with the TAC regimen (TAC/MPS group). MEASUREMENTS AND MAIN RESULTS: Both groups were followed for 24 months after transplantation for immunosuppressive regimen-associated and time-dependent occurrences of adverse events (AEs) and serious adverse events (SAEs). Before conversion from TAC to SRL, the cumulative incidence of AEs was 98%; 25% were SAEs. Gastrointestinal AEs (66%) and infections (58%) were the most frequent AEs. The incidences of TAC and MPS dose reductions due to AEs were 1.7% and 12%, respectively. After conversion, no significant differences were noted in the SRL/MPS group versus the TAC/MPS group in the cumulative incidences of AEs (100% vs. 98%) and SAEs (27% vs. 30%). The most common AEs were gastrointestinal (70% vs. 54%, p=0.23) and infection (77% vs. 73%, p=0.79) in the SRL/MPS versus TAC/MPS groups. The incidence of aphthous ulcer (28% vs. 0%, p=< 0.01), sinusitis (10% vs. 0%, p=0.01), dermatitis (15% vs. 3%, p=0.03), and dyslipidemia (35% vs. 14%, p=0.02) were higher in the SRL/MPS group compared with the TAC/MPS group. Cox proportion regression analysis showed a higher relative risk for gastrointestinal (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.2-3.01, p<0.05) and skin and subcutaneous tissue (HR 2.5, 95% CI 1.1-4.1, p<0.05) AEs in the SRL/MPS group compared with the TAC/MPS group. AE-related dose reductions occurred in 18.3% of patients receiving SRL and 3.3% of patients receiving TAC. MPS dose reductions due to AEs occurred in 11.7% of patients receiving SRL and 13.6% of patients receiving TAC. CONCLUSION: SRL/MPS treatment was associated with a time-dependent higher incidence of gastrointestinal and skin and subcutaneous tissue AEs, which occurred mainly during the first 6 months after conversion from TAC/MPS. Although the treatments with SRL or TAC after 3 months of transplantation showed different safety profiles, both regimens demonstrated adequate tolerability, with low rates of early discontinuation related to AEs.

Anti-trypanosomal phenolic derivatives from Baccharis uncinella.

Bioassay-guided fractionation of the EtOH extract of the aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to identification of two cinnamic acid derivatives (caffeic and ferulic acids), two flavones (hispidulin and pectolinaringenin) and a mixture of three chlorogenic acids (3,4-, 3,5- and 4,5-O-dicaffeoylquinic acids), which displayed in vitro anti-trypanosomal activity. Pectolinaringenin, hispidulin and caffeic acid showed activity against trypomastigotes of Trypanosoma cruzi, exhibiting 50% inhibitory concentration (IC50) values of 52, 81 and 56 microg/mL, respectively, while the chlorogenic acid mixture showed an IC50 value of 61 microg/mL. The flavonoids and cinnamic acid derivatives were evaluated for cytotoxicity against NCTC cells resulting in a 50% cytotoxic concentration (CC50) ranging from 33.82 to 129.1 microg/mL while the chlorogenic acids did not display cytotoxicity (CC50 >150 microg/mL). This is the first report of anti-trypanosomal activity of compounds from B. uncinella.