Pyoderma gangrenosum (PG) is a cutaneous ulcer developing so rapidly that may mimic a fulminating infection. The correct treatment is nonsurgical, and surgery may get the condition worse.1 FK-506 ointment (0.1% Protopic, Astellas Pharma AG, Fribourg) is usually indicated for inflammatory skin diseases, such as atopic dermatitis and psoriasis2 or for acute rejection reversal of human hand transplantation 3. A few reports of PG affecting the functions of hands can be found in the scientific literature and this report describes the first case treated by FK-506 ointment as an adjuvant therapy.
Aged ; Hand ; Humans ; Male ; Ointments ; Pyoderma Gangrenosum ; drug therapy ; pathology ; Tacrolimus ; administration & dosage

BACKGROUND: Topical tacrolimus is an effective anti-inflammatory therapy for acute and chronic states of atopic dermatitis (AD) in both adults and children. Topical tacrolimus has particular use at sensitive areas such as the face, anogenitals, and skin folds of neck and extremities. However, many AD patients also experience aggravated symptoms on trunk. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of topical tacrolimus for AD patients with truncal lesions. METHODS: AD patients with truncal lesions who were aged ≥2 years were recruited from 20 centres in Korea. They received treatment with topical tacrolimus ointment twice daily during 4 weeks. The primary end point was change of the local eczema area and severity index (EASI) of the trunk from baseline to day 28. The secondary end points were changes in the patient global assessment (PGA) score and itch visual analogue scale (VAS) score of the trunk between baseline and day 28. RESULTS: Two hundred and ninety-one patients were recruited, and 176 patients completed the full 4-week treatment course. By the end of the treatment, the mean local EASI of the trunk (2.2±4.71) was significantly decreased from that at baseline (4.71±4.03, p < 0.001). PGA (1.71±1.15) and itch VAS score of the trunk (2.61±2.19) on day 28 were also profoundly decreased compared with the baseline (2.96±1.07 and 5.15±2.47, respectively). No serious adverse events were observed during the study period. CONCLUSION: Topical tacrolimus is an effective and safe therapy for truncal lesions in AD patients.
Administration, Topical ; Adult ; Child ; Dermatitis, Atopic* ; Eczema ; Extremities ; Humans ; Korea ; Neck ; Skin ; Tacrolimus*

Modified Release (MR) tacrolimus is an extended release formulation of tacrolimus (Prograf (R) ) administered once daily in the morning. In healthy volunteers, the MR tacrolimus formulation given qd AM and Prograf administered twice daily (bid) have a similar exposure (AUC) and trough levels (Cmin), with a reduced peak level (Cmax). Subsequently, pharmacokinetic studies were performed in stable kidney and liver transplant recipients converted from Prograf bid to MR tacrolimus qd AM. The steady-state tacrolimus exposure and target trough level range of MR tacrolimus were equivalent to Prograf after a mg-for-mg daily dose conversion in these two groups of patients, and there is a high correlation of exposure to trough levels for both Prograf and MR tacrolimus, as well as significantly less intra-subject variability in exposure after conversion to MR tacrolimus. These results indicate that stable kidney and liver transplant recipients can be safely converted from standard Prograf twice daily dosing to the same mg- for-mg daily dose of MR tacrolimus once daily in the morning. Hopefully a once daily dosing regimen of tacrolimus can improve patient compliance while maintaining effective immunosuppression.
Delayed-Action Preparations ; Humans ; Immunosuppressive Agents/*administration & dosage/therapeutic use ; *Kidney Transplantation ; *Liver Transplantation ; Tacrolimus/*administration & dosage/therapeutic use

To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients, the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chromatography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharmacokinetic parameters. The mean C(max), t(max), and AUC((0-12))were (21.88+/-10.52) microg/ml, (1.20+/-0.95) h, and (52.546+/-13.215) microg.h/ml, respectively. The level of AUC((0-12)) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC((0-12)) showed statistically significant difference according to the patient's gender.
Adult ; Cyclosporine ; administration & dosage ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; pharmacokinetics ; Kidney Transplantation ; physiology ; Male ; Middle Aged ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Tacrolimus ; administration & dosage

OBJECTIVETo assess the efficacy and safety of topical tacrolimus for erosive oral lichen planus (EOLP).

METHODSLiteratures published up to December 2013 were searched from PubMed, Embase, CENTRAL, Chinese BioMedical Literature Database (CBM), and System for Information on Grey Literature in Europe (SIGLE). All randomized controlled trials (RCTs) of topical tacrolimus for EOLP which compared with other interventions or a placebo were considered in this Meta-analysis. Two researchers collected data independently. The assessment of methodological quality was based on Cochrane Handbook and the materials were analyzed with the software Revman 5.2.5. The primary outcome measures were the symptoms (e.g. pain, discomfort) complained by patients. The secondary outcome measures included the improvement rate of clinical signs assessed by the investigators and the incidence of adverse effects (e.g. clinical candidiasis).

RESULTSA total of 9 RCTs involving 476 patients were finally included. The pooled odds ratio (OR) of clinical improvement for topical tacrolimus vs. topical corticosteroids was 1.19 [95% confidence interval (CI): 0.64-2.22, I2: 44%]. Regarding to 0.1% tacrolimus and 0.03% tacrolimus, the pooled OR were 1.87 (95% CI: 0.60-5.82) and 1.47 (95% CI: 0.14-16.04) respectively in subgroup analysis. No serious adverse events were reported in topical tacrolimus group.

CONCLUSIONSThere was no evidence to support that topical tacrolimus for EOLP was more effective and safer than topical corticosteroids in this Meta-analysis. Clinical assessment criteria should be established and accepted by clinicians and researchers before further RCTs are undertaken.

Administration, Topical ; Humans ; Immunosuppressive Agents ; administration & dosage ; Lichen Planus, Oral ; drug therapy ; Randomized Controlled Trials as Topic ; Tacrolimus ; administration & dosage ; adverse effects

OBJECTIVETo investigate the antipruritic mechanisms of pimecrolimus cream for women facial dermatitis.

METHODSTopical pimecrolimus cream 1% was applied in 52 women patients with facial dermatitis. The Investigators Global Assessment (IGA) score, severity of pruritus (SP) scores, and a basic syntax and molecular substrate (molecular psychophysics) of nociception and pruriception established by temperature-sensitive transient receptor potential (TRP) channels were used to evaluate the clinical signs, severity of pruritus, and skin sensory phenomenon.

RESULTSThe IGA scores at day 1 and 4 of treatment and the SP score at day 1, 4, and 11 of treatment were significantly lower than the baseline scores before treatment (P < 0.05). Among these 52 patients, 28 (53.8%) showed positive capsaicin-like response (i.e., burning with consequent rapid amelioration of pruritus) at the application sites, 12 (23.1%) showed camphor-like response (i.e., warming with consequent rapid amelioration of pruritus), and 12 (23.1%) showed negative capsaicin-like response or negative camphor-like response.

CONCLUSIONSTreatment with pimecrolimus cream 1% can rapidly and effectively improve the signs and symptoms of facial dermatitis in adult women patients. Pimecrolimus cream 1% may act on the transient potential vanilloid 1 (TRPV1) receptor in the skin sensory afferents to induce capsaicin-like response or camphor-like response and then desensitizes TRPV1 and rapidly inhibits or alleviate itching.

Administration, Topical ; Adolescent ; Adult ; Antipruritics ; administration & dosage ; Dermatitis ; complications ; drug therapy ; Face ; Female ; Humans ; Middle Aged ; Pruritus ; drug therapy ; etiology ; Tacrolimus ; administration & dosage ; analogs & derivatives ; Young Adult

OBJECTIVETo retrospectively study and analyse the immune regulatory effect of Bailing Capsule (BLC, a dry powder preparation of Cordyceps sinensis mycelia) on patients after renal transplantation, its influences on various systems of organism, and to explore its possible acting mechanism.

METHODSIn accordance with the entry criteria, 67 recipients of renal homo-allograft were assigned to two groups. The 42 cases in the control group were treated with mycophenolate mofetil (MMF) plus cyclosporine A (CsA), or tacrolimus (FK506) plus prednisone (Pred); the 25 in the treated group treated with the chemotherapy the same as in the control group plus BLC. They were followed up for 48 weeks by checking up blood routine, urine routine, hepatic and renal function, total serum protein, serum albumin, uric acid, etc., and the dosage of immunoinhibitory used was recorded periodically.

RESULTSComparison showed no significant difference in graft survival rate, occurrence of reject reaction and renal function recovery between the two groups; but levels of urinary erythrocytes and leucocytes, blood alanine transaminase, aspartate amino transferase, uric acid, total bilirubin, direct bilirubin, as well as the incidence of infection were significantly lower, and serum total protein and albumin were significantly higher in the treated group (all P < 0.01); moreover, counts of erythrocyte and leukocyte from 12 to 48 weeks, T-lymphocyte from 4 to 48 weeks after transplantation were significantly higher in the treated group (P < 0.05 and P < 0.01), and the recovery appeared earlier, the dosage of CsA or FK506 used 12 weeks after operation was significantly lower in the treated group than in the control group (P < 0.05, P < 0.01).

CONCLUSIONSBLC could effectively protect liver and kidney, stimulate hemopoietic function, improve hypoproteinemia, as well as reduce the incidence of infection and the dosage of CsA and FK506 used, etc. Therefore, it is a useful drug for immunoregulation after organ transplantation.

Adult ; Capsules ; Cordyceps ; Cyclosporine ; administration & dosage ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Tacrolimus ; administration & dosage

This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.
Algorithms ; Bayes Theorem ; Database Management Systems ; Drug Monitoring ; methods ; Humans ; Immunosuppressive Agents ; administration & dosage ; pharmacokinetics ; Kidney Transplantation ; Models, Biological ; Tacrolimus ; administration & dosage ; pharmacokinetics

Angioplasty, Balloon, Coronary ; Coronary Artery Bypass ; Coronary Disease ; therapy ; Drug Delivery Systems ; Estradiol ; administration & dosage ; Everolimus ; Humans ; Paclitaxel ; administration & dosage ; Sirolimus ; administration & dosage ; analogs & derivatives ; Stents ; adverse effects ; Tacrolimus ; administration & dosage

The goal of this study is to investigate the population pharmacokinetics of oral tacrolimus in Chinese renal transplant patients and to identify possible relationship between covariates and population parameters. Details of drug dosage history, sampling time and concentration of 802 data points in 58 patients were collected retrospectively. Before analysis, the 58 patients were randomly allocated to either the model building group (n=41) or the validation group (n=17). Population pharmacokinetic data analysis was performed using the nonlinear mixed-effects model (NONMEM) program on the model building group. The pharmacokinetics of tacrolimus was best described by a one compartment model with first-order absorption and elimination. Typical values of apparent clearance (CL/F), apparent volume of distribution (V/F) were estimated. A number of covariates including demographic index, clinical index and coadministration of other drugs were evaluated statistically for their influence on these parameters. The final population model related clearance with POD (post operative days), HCT (haematocrit), AST (aspartate aminotransferase) and coadministration of nicardipine and diltiazem. Predictive performance of the final model evaluated with the validation group showed insignificant bias between observed and model predicted concentrations. Typical value of CL/F and V/F was 21.7 L x h(-1) and 241 L, inter-patient variability (RSD) in CL/F and V/F was 41.6% and 49.7%, respectively. The residual variability (SD) between observed and model-predicted concentrations was 2.19 microg x L(-1). The population pharmacokinetic model of tacrolimus in Chinese renal transplant patients was established and significant covariates on the tacrolimus model were identified.
Administration, Oral ; Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; blood ; pharmacokinetics ; Kidney Transplantation ; Male ; Metabolic Clearance Rate ; Middle Aged ; Models, Statistical ; Nonlinear Dynamics ; Retrospective Studies ; Tacrolimus ; administration & dosage ; blood ; pharmacokinetics ; Young Adult