Clinical Pharmacokinetics of Tacrolimus after the First Oral Administration in Renal Transplant Recipients on Triple Immunosuppressive Therapy

Abstract: Monitoring of tacrolimus blood concentration is of utmost importance in the management of renal transplant recipients because of Narrow Therapeutic Index and highly variable pharmacokinetics. The aim of this study was to detect inter‐patient pharmacokinetic variability of tacrolimus and to assess the predictability of individual tacrolimus concentrations at various times of the area under the curve (AUC) seeking to find the best sampling time to predict the exposure of tacrolimus in renal transplant recipients with triple therapy. This oral dose tacrolimus pharmacokinetics study was conducted in 18 Serbian renal transplant recipients on triple immunosuppressive therapy, including basiliximab. The first oral dose of tacrolimus (0.05 mg/kg) was given on day 5 post‐transplant; blood concentration was measured by microparticle enzyme immunoassay method. Associations between each sampling time‐point of concentrations and AUC₁₂ were evaluated by Pearson correlation coefficients. Abbreviated sampling equations were derived by multiple, stepwise regression analyses. The variance in the strength of association between predicted AUC (AUC_p) and AUC₁₂ was reflected by linear regression coefficients. AUC₁₂ showed remarkable inter‐individual variations after the first oral dose of tacrolimus. The area of the maximum AUC was four times higher than that of the minimum AUC. C₄ seems to be an indicator of total body exposure to tacrolimus. Alternatively, the concentrations at 1.5, 4 and 8 hr as an abbreviated AUC were as good a predictor as a full pharmacokinetic study. Our results show a significant difference between men and women. A three‐point sampling method seemed to be the best abbreviated AUC for a cost‐effective tacrolimus monitoring strategy.     

Use of cultivation-dependent and -independent techniques to assess contamination of central venous catheters: a pilot study

Background  

Catheters are the most common cause of nosocomial infections and are associated with increased risk of mortality, length of hospital stay and cost. Prevention of infections and fast and correct diagnosis is highly important.     

Lichen planus and other cutaneous manifestations in chronic hepatitis C: pre- and post-interferon-based treatment prevalence vary in a cohort of patients from low hepatitis C virus endemic area

Background Several controversies exist regarding the relationship between hepatitis C virus (HCV) infection and some cutaneous manifestations, lichen planus (LP) in particular. Objectives To determine the prevalence of LP and other cutaneous manifestations in a cohort of patients infected with HCV from low HCV endemic area of Slovenia, to correlate findings with chosen biological variables and to assess the role of interferon (IFN)‐based treatment of HCV infection in cutaneous manifestations. Methods A total of 171 consecutive HCV‐seropositive patients and 171 HCV‐seronegative age‐ and gender‐matched controls were studied prospectively. Prevalence of cutaneous manifestations, comparison between study patients and controls and correlation of skin findings with demographic, biochemical, virological and liver histologic findings as well as IFN‐based therapy were assessed. Results Overall presence of LP in HCV‐seropositives was 2.3%; although LP was not found in controls, the difference was not statistically significant (P = 0.123). Significantly higher than in controls was the prevalence of pruritus (31.0%, P < 0.001), dry skin (16.4%, P < 0.001) and hair loss (9.9%, P < 0.001). In IFN‐based treatment naïves, skin findings were more frequent compared with controls, but not significantly, with no correlation to chosen biological variables. Current IFN‐based treatment was significantly connected to pruritus (P < 0.001) and dry skin (P < 0.001). Compared with treatment naïves, in post‐treated patients pruritus (odds ratio, 19.13; 95% confidence interval, 6.85–53.42; P < 0.001), dry skin (odds ratio, 4.21; 95% confidence interval, 1.44–12.31; P < 0.001) and hair loss (P < 0.001) were significantly more common. Conclusions LP was not significantly related to HCV infection. Prevalence of pruritus, dry skin and hair loss was significantly higher in post‐compared with pre‐treated patients. The role of IFN in post‐treatment persistence of skin manifestations needs to be assessed.     

Oxidative stress,NOx/l-arginine ratio and glutathione/glutathione S-transferase ratio as predictors of ‘sterile inflammation’ in patients with alcoholic cirrhosis and hepatorenal syndrome type II

Continuous intake of alcohol leads to liver cirrhosis because of imbalance of oxidative stress/antioxidative defense and chronic ‘sterile inflammation’. Hepatorenal syndrome (HRS) is the most severe complication of liver cirrhosis. The aim of our study was to assess: (1) the oxidative stress/antioxidative defense markers such as malondialdehyde (MDA), oxidative glutathione (GSH) and glutathione S-transferase (GST), (2) inflammation [C-reactive protein (CRP)], and (3) nitrate/nitrite levels (NOx) and its substrate L-arginine level. The study enrolled three groups: a group with cirrhosis and HRS (48 patients), a group with cirrhosis without HRS (32 patients), and a control group (40 healthy blood donors). All the patients with cirrhosis and HRS had type II HRS. MDA concentration was significantly higher in the groups with cirrhosis with and without HRS. Significant positive correlation was documented between the MDA level and de Ritis coefficient (AST/ALT), a marker of liver damage severity; between MDA and inflammation (CRP); between MDA and NOx concentration in the groups with cirrhosis with and without HRS. The correlation between MDA and creatinine level was significant in the group with HRS. The levels of GSH and GST were significantly lower in the groups with cirrhosis with and without HRS. The results of the study revealed that an increase in MDA and NOx concentration, along with decreased values of antioxidative defense and L-arginine, may indicate that liver damage can have an influence on progression to renal failure.     

Clinical predictors of success and failure for lumbar facet radiofrequency denervation

OBJECTIVE: To determine the clinical factors associated with the success and failure of radiofrequency denervation of the lumbar facet joints. METHODS: Clinical data were garnered from 3 academic medical centers on 192 patients with low back pain who underwent radiofrequency denervation after a positive response to diagnostic blocks. Success was defined as >/=50% pain relief lasting at least 6 months. Factors evaluated for their association with outcome included duration of pain, opioid use, symptom location, paraspinal tenderness, pain exacerbated by extension/rotation (ie, facet loading), MRI abnormalities, diabetes, smoking, scoliosis, obesity, prior surgery and levels treated. RESULTS: The only factor associated with a successful outcome was paraspinal tenderness. Variables that correlated with treatment failure were 'facet loading,' long duration of pain, and previous back surgery. CONCLUSIONS: It is counterproductive to use 'facet loading' as the sole basis for choosing patients for facet interventions. In patients at high risk for treatment failure, taking additional steps to reduce the rate of false-positive screening blocks may improve outcomes.