Analysis of correlation between plasma trough level and response of generic imatinib in the treatment of Chinese patients with chronic myeloid leukemia / 中华血液学杂志

Objective@#To analyze the correlation between plasma trough level of generic imatinib and its metabolism and clinical outcomes in Chinese patients with chronic myeloid leukemia in chronic phase (CML-CP) .@*Methods@#The 21 patients with CML-CP who enrolled in a clinical trial YMTN 1.0 from Oct 11th, 2012 to May 8th, 2013 and received generic imatinib were as study subjects. The correlation between steady plasma trough levels of imatinib and its metabolism with clinical response, age, weight and body surface area (BSA) were evaluated.@*Results@#①The mean steady plasma trough level of generic imatinib and its metabolism was (1 185.07±417.91) μg/L and (251.53±76.50) μg/L, respectively. ②Age, weight and BSA has no significant effects on plasma trough level of generic imatinib and its metabolism (P>0.05) . ③Patients with steady plasma trough level of generic imatinib more than 1 000 μg/L are possible to have higher major molecular response (MMR) /complete molecular response (CMR) rate than those below 1 000 μg/L (42% vs 0, P<0.05) .@*Conclusion@#Plasma trough levels of generic imatinib varied in CML patients. The steady plasma trough levels of generic imatinib is maybe related to molecular response in CML patients.

The influencing factors achieving target vancomycin trough level in critically ill patients / 中华内科杂志

Objective To assess the rate achieving the target vancomycin trough level (VTL) and its influencing factors in critically ill patients.Methods The retrospective observational study recruited adult patients treated with intravenous vancomycin in the intensive care unit (ICU) at Zhongda Hospital from January 2015 to December 2017.Serum VTL was tested at steady state.Patients' demographics,the sites of infection,microbial culture results,the severity of illness,laboratory data and vancomycin regimen were obtained at the baseline.The rate achieving target VTL (15-20 mg/L) was analyzed based on renal function.Linear regression was performed to determine the influencing factors of VTL.Results A total of 85 patients were enrolled,among whom only 23.5％ (20/85) achieved the target VTL.In patients with normal renal function,the achieving rate was only 11.4％ (4/35),and 80.0％ (28/35) was lower than the target trough level multiple linear regression analysis showed that procalcitonin (PCT),estimated glomerular filtration rate (eGFR) and acute physiology and chronic health disease classification system Ⅱ (APACHE Ⅱ) score were independent factors associated with VTL.Conclusion Achieving target VTL in critically ill patients is not satisfactory.Further study to optimize the administration is needed to facilitate prompt attainment of target VTL.

Comparison of Transplant Outcomes for Low-level and Standard-level Tacrolimus at Different Time Points after Kidney Transplantation

BACKGROUND: Optimal tacrolimus (TAC) trough levels for different periods after kidney transplantation (KT) has not been definitely established. This study aimed to investigate transplant outcomes of low-level (LL) and standard-level (SL) TAC according to post-transplant period. METHODS: A total of 278 consecutive kidney transplant recipients (KTRs) receiving TAC-based immunosuppression were divided into LL and SL-TAC groups (4–7 and 7–12 ng/mL for 0–2 months, 3–6 and 6–10 ng/mL for 3–6 months, 2–5 and 5–8 ng/mL for 7–12 months, respectively) according to TAC trough level at each period. We compared estimated glomerular filtration rate (eGFR), biopsy-proven acute rejection (BPAR), de novo donor-specific antibody (dnDSA), calcineurin inhibitor (CNI) toxicity, opportunistic infection, and allograft survival. RESULTS: SL-TAC group showed significantly higher mean eGFR at 0–2 months than LL-TAC group (72.1 ± 20.3 vs. 64.2 ± 22.7 mL/min/1.73m2; P = 0.003). Incidence of BPAR at 7–12 months was significantly lower in SL-TAC group than in LL-TAC group (0.0% vs. 3.9%; P = 0.039). Patients with persistent SL-TAC lasting 12 months showed higher eGFR at 7–12 months than those with persistent LL-TAC (65.5 ± 13.0 vs. 57.9 ± 13.9 mL/min/1.73m2; P = 0.007). No significant differences in dnDSA, CNI toxicity, serious infections, or allograft survival were observed. CONCLUSIONS: Maintenance of proper TAC trough level after 6 months could reduce BPAR without adverse drug toxicities in KTRs. Moreover, persistent SL-TAC during the first year after KT might have a beneficial effect on a trend for a lower incidence of dnDSA and better renal allograft function.

Trough level of infliximab is useful for assessing mucosal healing in Crohn's disease: a prospective cohort study

BACKGROUND/AIMS: Decreased trough levels of infliximab (TLI) and antibodies to infliximab (ATI) are associated with loss of response (LOR) in Crohn's disease. Two prospective studies were conducted to determine whether TLI or ATI better correlates with LOR (Study 1), and whether TLI could become a predictor of mucosal healing (MH) (Study 2). METHODS: Study 1 was conducted in 108 patients, including those with LOR and remission to compare ATI and TLI in discriminating the 2 conditions based on receiver operating characteristic (ROC) curve analyses. Study 2 involved 35 patients who were evaluated endoscopically. RESULTS: In Study 1, there were no differences between the 2 assays in ROC curve analyses; the TLI cutoff value for LOR was 2.6 µg/mL (sensitivity, 70.9%; specificity, 79.2%), and the ATI cutoff value was 4.9 µg/mL (sensitivity, 65.5%; specificity, 67.9%). The AUROC (area under the ROC curve) of TLI was greater than that of ATI. AUROC was useful for discriminating between the 2 conditions. In Study 2, the TLI was significantly higher in the colonic MH group than in the non-MH group (2.7 µg/mL vs. 0.5 µg/mL, P=0.032). CONCLUSIONS: TLI is better than ATI for clinically diagnosing LOR, and a correlation was observed between TLI and colonic MH.

Clinical Use of Measuring Trough Levels and Antibodies against Infliximab in Patients with Pediatric Inflammatory Bowel Disease

BACKGROUND/AIMS: The clinical use of measuring infliximab (IFX) trough levels (TLs) and antibodies against IFX (ATIs) in patients with pediatric inflammatory bowel disease (IBD) remains unclear. We propose measuring these variables to create individual IFX treatment strategies for patients with pediatric IBD. METHODS: This retrospective study was conducted in pediatric patients with IBD who received IFX from July 2009 to June 2014. RESULTS: Samples were available from 39 patients with pediatric IBD. A significant difference was observed in IFX TLs in 16 patients who were in clinical remission (group A) after IFX therapy (median, 3.99 μg/mL; interquartile range [IQR], 0.30 to 21.96) compared to 23 patients who had a poor response to treatment (group B) (median, 0.88 μg/mL; IQR, 0.00 to 6.80, p=0.002). In group B, 21 patients underwent empiric intensification of IFX treatment. After dose intensification, 17 patients had an improved response to treatment. Four patients still had no response to dose intensification. Therefore, these patients were switched to other biologics. CONCLUSIONS: Patients who had poor responses and subtherapeutic IFX TLs had an improved response to dose intensification. Patients who had ATIs were likely to continue to have no response after dose intensification. Therefore, tailoring individual IFX treatments based on IFX TLs, ATIs, and the clinical response should be considered.

Comparison of Cyclosporine in Soft Gelatine Capsule and Microemulsion Cyclosporine in Renal Transplant Recipients / 대한이식학회지

A new microemulsion formulation of cycloporine(CsA) has been recently used in Korean renal transplants. We compared the clinical effect and the trough levels of microemulsion cyclosporine(M-CsA) as opposed to conventional CsA in soft gelatine capsule(C-CsA). In the study for hospitalized post-operative patients, 58 patients were divided into two groups; the C-CsA(control) group(n=23) received C-CsA, and the M-CsA group(n=28) received M-CsA after transplantation. In the study for stable OPD patients, 32 patients were divided into two groups. The C-CsA(control) group(n=16) did not change the type of CsA and continued C-CsA medication after Sep. 1994, M-CsA group(n=16) switched from C-CsA to M-CsA in Sep. 1995. In postoperative hospitialized patients, mean trough levels were not different between the two groups with CsA dosage (9mg/kg - 5mg/kg), although the M-CsA group had higher trough levels with 10mg/Kg CsA dosage than the control group. In OPD patients, there was no significant change in CsA dosage in both groups during the 6 month period. Mean trough levels, 6 months after conversion, were lower in the M-CsA group than in the control group. In the M-CsA group who received the same dose as a preconversion dose, mean trough levels at 2, 3, 4, 5, 6 months were lower than the preconversion level, although control groups had lower trough levels only at 5 months. Serum creatinine levles were significantly decreased in the M-CsA OPD patients. From these results, we couldn't find a dose saving effect of M-CsA in our patients, it is much desirable to study the pharmacokinetics of M-CsA and C-CsA in Korean renal transplants.