Rituximab in the management of acute lymphoblastic leukemia

Introduction: The anti-CD20 chimeric monoclonal antibody rituximab has revolutionized the treatment of B-cell malignancies, significantly improving patient clinical outcome. Recently, some single-group studies have suggested that adding rituximab to chemotherapy can improve the outcome of CD20-positive B-cell acute lymphoblastic leukemia (ALL) patients.

Areas covered: An overview of the current insights of rituximab in adult ALL patients is presented here. In particular, we focused on results of multicenter randomized phase III trial (GRAALL-2005 – Group for Research on Adult Acute Lymphoblastic Leukemia) that evaluated the benefit of associating rituximab to chemotherapy in Ph-negative, B-lineage ALL expressing the CD20 antigen.

Expert opinion: Data from clinical trials confirm that rituximab enhances the efficacy of chemotherapy without additive toxicity in ALL. However, results of GRAAL 2005 study represent only a modest incremental improvement in the treatment of ALL. Other promising compounds as single agent or in combination with chemotherapy are currently in different stages of clinical development. The GRAALL 2005 study sets the stage for other prospective studies which will further elucidate the role of monoclonal antibodies in the management of ALL.     

Treatment Avenues in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Split-gender Pharmacogenomic Study of Gene-expression Modules

PurposeMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisymptom illness impacting up to 1 million people in the United States. As the pathogenesis and etiology of this complex condition are unclear, prospective treatments are limited. Identifying US Food and Drug Administration–approved drugs that may be repositioned as treatments for ME/CFS may offer a rapid and cost-effective solution.MethodsHere we used gene-expression data from 33 patients with Fukuda-defined ME/CFS (23 females, 10 males) and 21 healthy demographically comparable controls (15 females, 6 males) to identify differential expression of predefined gene-module sets based on nonparametric statistics. Differentially expressed gene modules were then annotated via over-representation analysis using the Consensus Pathway database. Differentially expressed modules were then regressed onto measures of fatigue and cross-referenced with drug atlas and pharmacogenomics databases to identify putative treatment agents.FindingsThe top 1% of modules identified in males indicated small effect sizes in modules associated with immune regulation and mitochondrial dysfunction. In females, modules identified included those related to immune factors and cardiac/blood factors, returning effect sizes ranging from very small to intermediate (0.147 < Cohen δ < 0.532). Regression analysis indicated that B-cell receptors, T-cell receptors, tumor necrosis factor α, transforming growth factor β, and metabolic and cardiac modules were strongly correlated with multiple composite measures of fatigue. Cross-referencing identified genes with pharmacogenomics data indicated immunosuppressants as potential treatments of ME/CFS symptoms.ImplicationsThe findings from our analysis suggest that ME/CFS symptoms are perpetuated by immune dysregulation that may be approached via immune modulation–based treatment strategies.     

Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically Relevant Phenotyping of Women With Chronic Fatigue Syndrome

Purpose

The complex and varied presentation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has made it difficult to diagnose, study, and treat. Its symptoms and likely etiology involve multiple components of endocrine and immune regulation, including the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, and their interactive oversight of immune function. We propose that the persistence of ME/CFS may involve changes in the regulatory interactions across these physiological axes. We also propose that the robustness of this new pathogenic equilibrium may at least in part explain the limited success of conventional single-target therapies.

Practice Nurses' views of their role in the management of Chronic Fatigue Syndrome/Myalagic Encephalitis: a qualitative study

Background  

NICE guidelines suggest that patients with Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME) should be managed in Primary Care. Practice Nurses are increasingly being involved in the management of long-term conditions, so are likely to also have a growing role in managing CFS/ME. However their attitudes to, and experiences of patients with CFS/ME and its management must be explored to understand what barriers may exist in developing their role for this group of patients. The aim of this study was to explore Practice Nurses' understanding and beliefs about CFS/ME and its management.     

Association Between High NK-Cell Count and Remission of Primary Membranous Nephropathy: A Retrospective Chart Review and Pilot Study

PurposePrimary membranous nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. Rituximab monotherapy has emerged as a front-line treatment for patients with PMN, but potential markers for predicting the response to rituximab are unknown.MethodsIn this single-arm retrospective pilot study, 48 patients with PMN without previous immunosuppressive therapy were enrolled. All patients were treated with rituximab and were followed up for at least 6 months. The primary end point was the achievement of complete or partial remission at 6 months. The subsets of lymphocytes were collected at baseline, 1 month, 3 months and 6 months to identify prognostic factors for achieving remission of PMN with rituximab therapy.FindingsA total of 58.3% of patients (28/48) achieved remission. Lower serum creatinine, greater serum albumin, and greater phospholipase A2 receptor antigen detected in kidney biopsy at baseline were found in the remission group. After multiple adjustments, a high percentage of natural killer (NK) cells at baseline, especially ≥15.7%, was strongly associated with remission (relative risk = 1.62; 95% CI, 1.00–2.62; P = 0.049), and patients with a response to rituximab had a greater mean percentage of NK cells during the follow-up period compared with nonresponders. Analysis using a receiver operating characteristic curve indicated prognostic value of the NK-cell percentage at baseline, with an area under the curve of 0.716 (95% CI, 0.556–0.876; P = 0.021).ImplicationsThe findings from this retrospective pilot study suggest that a high percentage, especially ≥15.7%, of NK cells at baseline might predict a response to rituximab treatment. These findings provide a basis for designing larger-scale studies to test the predictive value of NK cells in patients with PMN undergoing rituximab treatment.     

Rituximab biosimilar CT-P10 for the treatment of rheumatoid arthritis

ABSTRACT

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by long-standing inflammation in multiple joints. Rituximab, a monoclonal antibody, which binds to CD20, is effective in suppressing disease activity and preventing joint damage in RA. CT-P10 was developed as a biosimilar of rituximab and approved for use to treat hematologic malignancies and immune diseases including RA.

Area covered: This article describes the need for this biosimilar and summarizes the non-clinical studies verifying the physicochemical and biologic similarities and the clinical studies confirming the clinical similarity of CT-P10 to rituximab in patients with RA.

Expert opinion: CT-P10 had been evaluated and proven the efficacy and safety in RA in Phase I and III randomized controlled trial with extension studies including a switching regimen. Therefore, CT-P10 is recommended in the treatment of RA.     

Brainstem perfusion is impaired in chronic fatigue syndrome

We looked for brain perfusion abnormalities in patients withmyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).An initial pilot study revealed widespread reduction of regionalbrain perfusion in 24 ME/CFS patients, compared with 24 normalvolunteers. Hypoperfusion ofthe brainstem (0.72±0.05vs. 0.80±0.04, p<0.0001) was marked and constant.We then tested whether perfusion to the brainstem in ME/CFSpatients differs from thatin normals, patients with major depression,and others with epilepsy. Data from a total of 146 subjectswere included in the present study: 40 normal volunteers, 67patients with ME/CFS(24 in the pilot study, 16 with no psychiatricdisorders, 13 with ME/CFS and depression, 14 with ME/CFS andother psychiatric disorders), 10 epileptics, 20 young depressedpatientsand 9 elderly depressed individuals. Brain perfusionratios were calculated using ⁹⁹Tc^m-hexamethylpropylene amineoxime (⁹⁹Tc^m- HMPAO) and single-photon emission tomography (SPET)with a dedicated three-detector gamma camera computer/system(GE Neurocam). Brainstem hypoperfusion was confirmed in allME/CFS patients. Furthermore, the 16 ME/CFS patients with nopsychiatric disorders and the initial 24 patients inthe pilotstudy showed significantly lower brainstem perfusion (0.71$0.03)than did depressed patients (0.77$0.03; ANOVA, p<0.0001).Patients with ME/CFS have a generalized reduction of brain perfusion,with a particular pattern of hypoperfusion of the brainstem.     

Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.     

A comparative study of Thai massage and muscle energy technique for chronic neck pain: A single-blinded randomized clinical trial

BackgroundMyofascial pain syndrome (MPS) is the most common form of muscle disorders. Traditional Thai massage (TM) and muscle energy (ME) technique have been used to treat patients with MPS for long time but head-to-head comparisons of these interventions have not been established.AimThe aim of the current study was to compare the effects of TM and the ME technique on pain intensity (PI), pressure pain threshold (PPT), neck disability (ND), and neck flexion range of motion (NFROM) in patients with chronic neck pain associated with myofascial trigger points (MTrPs).DesignA randomized, single-blinded clinical trial.SettingDepartment of Physical Therapy, School of Integrative Medicine, Mae Fah Luang University.PopulationForty-five patients with chronic neck pain associated with MTrPs were recruited.MethodsThe patients were randomly allocated to the TM, ME, or control groups, with each having eight treatment sessions over a period of two weeks. PI, PPT, ND, and NFROM were assessed before, immediately after the first treatment session, and one day after the last treatment session.ResultsBased on the results, both TM and the ME technique resulted in a significant improvement in all parameters (p < 0.05) compared to the control group. Additionally, no significant difference was observed between TM and the ME technique in all parameters.ConclusionsThe application of TM or the ME technique can be a practical alternative approach for the treatment of chronic neck pain associated with MTrPs.     

Ultra-low dose rituximab for refractory pemghigus vulgaris: a pilot study

ABSTRACT

Background: Pemphigus vulgaris is an autoimmune blistering disease affecting the skin and mucous membranes. Current treatments for pemphigus vulgaris include anti-inflammatory and immunosuppressive agents. Rituximab, an anti-CD20 monoclonal antibody, has been shown to be effective for the treatment of pemphigus vulgaris. However, the optimal dosage of rituximab for the treatment of this autoimmune bullous disease has not been clearly defined.

The aim of this study was to investigate the clinical efficacy and adverse effects of an ultra-low dosage regimen of rituximab for pemphigus vulgaris.

Methods: We performed a prospective non-randomized open case series including eight patients affected by pemphigus vulgaris. Patients were treated with an ultra-low dosage of rituximab (a single infusion of 200 mg).

Results: All patients had a positive response after infusion. At the end of the follow-up period, 5 patients achieved a complete remission and 3 a partial remission. Except for one case of sepsis due to Citrobacer freundii and a pneumonia due to Haemophilus influenzae, no adverse events were documented in our patients.

Conclusions: Data from our study suggest that an ultra-low dosage of rituximab could be an effective treatment for pemphigus vulgaris. Consequently, there is a need for a larger, confirmatory, randomized, multicenter trial.     

Vitamin D Provides Benefit Based on the Proinflammatory Effects of Homocysteine in Elderly Patients With Type 2 Diabetes Mellitus

PurposeIt is unclear whether vitamin D provides any benefit against the pro-inflammatory effects of homocysteine in elderly patients with type 2 diabetes mellitus (T2DM).MethodsWe compared lymphocyte counts for CD3, CD19, CD4, and CD8 subsets between elderly (age ≥65 years) T2DM patients (n = 5098) and nondiabetes control subjects (n = 20,590) based on the serum concentrations of homocysteine and total vitamin D (calcidiol + calcifediol [total vitamin D, TVD]; <20, 20-30, and >30 ng/mL).FindingsSignificant variation in CD19 (P = 0.019), CD4 (P = 0.015), and CD8 (P < 0.001) were associated with serum TVD in T2DM patients with homocysteine ≤15 μmol/L, whereas CD3 (P = 0.003) and CD8 (P = 0.019) varied in control subjects with homocysteine ≤15 μmol/L. In T2DM patients with high homocysteine (>15 μmol/L) levels, significant variation based on serum TVD occurred in CD19 only (P = 0.024), whereas CD3 (P = 0.016) and CD4 (P = 0.001) varied in control subjects with high homocysteine concentrations.ImplicationsSerum TVD influences variation in CD3, CD19, CD4, and CD8 lymphocyte subsets based on the serum homocysteine concentration in elderly T2DM patients and nondiabetic individuals with moderate to high homocysteine concentrations. The effect of TVD is partially attenuated in individuals with high homocysteine concentrations, with greater attenuation occurring in patients with T2DM. Differences in the variation of lymphocyte subsets between nondiabetes subjects with moderate homocysteine concentrations and those with high homocysteine concentrations constitute a shift from CD8-positive cells to CD4-positive cells, suggesting a change in TH1/TH2 balance based on TVD and homocysteine concentrations that is absent in diabetes cases with high homocysteine concentrations.     

Outcomes and adverse effects of extremely high dose insulin infusions in ICU patients

PurposeDescribe the characteristics, hospital course, and outcomes of adult ICU patients receiving extremely high dose insulin infusions compared to those with lower insulin requirements.Materials and methodsRetrospective observational study of 128 adult ICU patients receiving IV insulin infusions at a large academic medical center. Extremely high dose insulin infusions were defined as maximum rate ≥ 35 units/h. The primary endpoint was rate of hypoglycemia (BG < 70 mg/dL) and time to glucose control. A post-hoc matching analysis was performed for baseline imbalances.ResultsAnalysis included 32 patents with extremely high dose insulin infusions and 96 patients without, and most had a goal BG 100–150 mg/dL. Patients in the extreme group were more likely to have type 2 diabetes, a higher median hemoglobin A1c, preadmission insulin, be admitted for a medical reason, and receive inpatient steroids. The extreme group were more likely to experience hypoglycemia (<70 mg/dL, 63% v. 34%, p = 0.005), longer time to glucose control (19.8 h v. 5.7 h, p < 0.001) and higher mortality (34% v. 15%, p = 0.014).ConclusionsICU patients with extremely high dose insulin infusions had more hypoglycemia and took longer to achieve glucose targets compared to those with lower requirements. An individualized approach may be required for appropriate management.     

A retrospective observational study of rituximab treatment in multiple sclerosis patients in Cyprus

Objective: The objective of this study was to evaluate the efficacy and safety of rituximab (RTX) treatment given off-label to Cypriot patients with multiple sclerosis (MS).

Methods: Clinical data from 30 MS patients ever treated with off-label RTX until mid-2018 at the Cyprus Institute of Neurology and Genetics were retrospectively collected and reviewed. The heterogeneous patient cohort included patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS). Outcome data (relapse rate and EDSS progression) as well as adverse effects for patients with a follow-up period of >12 months (n = 13) were recorded.

Results: Following RTX administration, all patients with RRMS remained relapse free and had a stable or slightly improved EDSS score (mean EDSS before treatment = 6, mean EDSS at 12 months = 4.75). Patients with SPMS had a significant reduction in their relapse rate and a stabilization or slight improvement of their EDSS scores (mean EDSS before treatment = 6.25, mean EDSS at 12 months = 5.5). Only one of the patients with PPMS had a follow-up period of >12 months and his EDSS score remained unchanged. Rituximab infusions were generally well tolerated; there were only seven grade 3 or 4 adverse events recorded.

Conclusion: Our results are in agreement with larger retrospective studies in which it was demonstrated that RTX was well tolerated and effective in treating RRMS and SPMS patients by reducing relapse rate and stabilizing disease.     

Is Splenectomy Necessary for Immune Thrombocytopenic Purpura? The Role of Rituximab in Patients With Corticosteroid Resistance in a Single-Center Experience

Background

Corticosteroid therapy followed by splenectomy for immune thrombocytopenic purpura (ITP) is the standard practice. Rituximab is mostly used in patients with chronic refractory ITP who have failed multiple previous treatments, including splenectomy.

Objective

We explored the potential role of rituximab as an early therapeutic option for patients with corticosteroid-resistant ITP who preferred to avoid splenectomy in favor of other treatment.

Methods

Twenty-five patients with corticosteroid-resistant ITP were treated with rituximab between May 1, 2009, and June 30, 2012, at a single center. Rituximab was administered at 100 mg/m² on days 7, 14, 21, and 28. The response to rituximab therapy and adverse effects were observed.

Results

Complete remission was achieved in 19 patients (76%), partial remission in 3 patients (12%), and minimal response in none of the patients; 1 patient was considered a treatment failure (4%). Two patients (8%) were lost to follow-up. Twenty-two patients (88%) achieved a platelet count >50×10⁹/L. The median time from administration of the first rituximab dose to partial remission was 2 months (range, 0.7–3 months) for all the patients. Response classified as sustained was achieved in 21 patients (84%). No serious adverse effects were observed during rituximab therapy.

Conclusions

Rituximab therapy is effective and safe for patients with corticosteroid-resistant ITP before splenectomy, resulting in high complete remission and overall response rates. A multicenter study with a larger sample should be performed to further explore the role of rituximab therapy.     

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

The safety and efficacy of relebactam/imipenem/cilastatin in Japanese patients with complicated intra-abdominal infection or complicated urinary tract infection: A multicenter,open-label,noncomparative phase 3 study

IntroductionRelebactam, a novel class A/C β-lactamase inhibitor developed as a fixed-dose combination with imipenem/cilastatin, restores imipenem activity against imipenem-nonsusceptible gram-negative pathogens.MethodsThis phase 3, multicenter, open-label, noncomparative study (NCT03293485) evaluated relebactam/imipenem/cilastatin (250 mg/500 mg/500 mg) dosed every 6 h for 5–14 days in Japanese patients with complicated intra-abdominal infections (cIAIs) or complicated urinary tract infections (cUTIs), including those with secondary sepsis. Sepsis was defined as an infection-induced systemic inflammatory response syndrome, with a documented positive blood culture; patients meeting these protocol-defined criteria were evaluated for efficacy against sepsis.ResultsOf 83 patients enrolled, 81 patients (cIAI, n = 37; cUTI, n = 44) received ≥1 dose of study treatment. Escherichia coli was the most common baseline pathogen isolated in both patients with cIAI and cUTI. Adverse events (AEs) were reported in 74.1% (n = 60/81) of patients, and drug-related AEs occurred in 18.5% (n = 15/81). The most common AEs were diarrhea and nausea (8.6%). Serious AEs occurred in nine patients, including one death, but none were considered treatment related. The primary efficacy endpoint for patients with cIAI was clinical response at end of treatment (EOT) in the microbiologically evaluable (ME) population, and for patients with cUTI was microbiological response at EOT in the ME population. The proportion of cIAI and cUTI patients achieving favorable responses were 85.7% (n = 24/28) and 100.0% (n = 39/39), respectively. All patients with sepsis (cIAI, n = 1; cUTI, n = 5) achieved a favorable composite clinical and microbiological response at EOT.ConclusionsA favorable safety and efficacy profile for relebactam/imipenem/cilastatin was observed in Japanese patients with cIAI and cUTI.     

Serum carotenoids in relation to risk factors for development of atherosclerosis

ObjectiveTo explore associations between serum carotenoids and risk factors for development of atherosclerosis.Design and methodsWe studied 40 early atherosclerosis patients without clinical cardiovascular events and comparable healthy controls aged 45–68 years. Intima-media thickness (IMT) and arterial stiffness were simultaneously measured by carotid ultrasonography, and serum carotenoids and cytokines were determined by high-pressure liquid chromatograph (HPLC) and ELISA kits respectively. We evaluated the associations between serum carotenoids, early atherosclerosis and serum cytokines.ResultsSerum concentrations of lutein and zeaxanthin in early atherosclerosis patients were significantly lower than those of control subjects. PCA logistic analysis found that serum carotenoids were associated with decreased risk of atherosclerosis. In contrast, blood pressure, body mass index and serum triglyceride were positively related to the risk of atherosclerosis. Ridge regression analysis revealed that serum carotenoids were associated with inflammatory cytokines and apoE. More specifically, serum lutein was inversely associated with IL-6 (P < 0.001) and positively associated IFN-γ (P = 0.002). In contrast, zeaxanthin had a significant negative association with VCAM-1 (P = 0.001) and apoE (P = 0.022) .Lycopene was inversely associated with VCAM-1(P = 0.011) and LDL (P = 0.046).ConclusionsThe results suggested that early atherosclerosis patients had lower serum concentrations of lutein and zeaxanthin than healthy subjects. Serum carotenoids were associated with reduced risk of atherosclerosis. The associations between serum carotenoids and inflammatory cytokines may help to explain the possible protective effects of carotenoids on atherosclerosis.     

High serum substance P levels and mortality after malignant middle cerebral artery infarction

PurposePreviously our team found higher serum substance P concentrations at day 1 of a malignant middle cerebral artery infarction (MMCAI) in non-surviving than in surviving patients. Thus, the objective of this study was to determine whether serum substance P levels during the first week of MMCAI could predict mortality.MethodsWe included patients with MMCAI defined as computed tomography findings of acute infarction in at least of 50% of the territory and Glasgow Coma Scale ≤8. We determined serum concentrations of substance P on days 1, 4 and 8 of MMCAI. Thirty-day mortality was the study end-point.ResultsSerum substance P concentrations at days 1 (p < .001), 4 (p < .001), and 8 (p = .001) of MMCAI in non-surviving (n = 34) were higher than in surviving patients (n = 34). Receiver operating characteristic analyses showed that serum substance P concentrations at days 1, 4, and 8 of MMCAI had an area under curve (95% confidence intervals) to predict 30-day mortality of 0.77 (0.66–0.87; p < .001), 0.82 (0.69–0.91; p < .001) and 0.85 (0.72–0.94; p < .001) respectively.ConclusionsThe two new findings of our study are that non-surviving MMCAI patients showed higher serum substance P levels at day 1, 4 and 8 than surviving, and that those levels could predict 30-day mortality.     

Clinical pharmacokinetics of oral azithromycin in epididymal tissue

ObjectivesChlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis.MethodsPatients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue.ResultsA total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue.ConclusionsThe penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.