This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability two cyclosporine (CsA) formulations, emulsion capsules oral solution for microemulsion cyclosporine, in postoperative management renal transplant patients. Of 101 patients, aged 18 to 65, who entered study, 89 were evaluable pharmacokinetics. Initial dosage 10 mg/kg per day, administered twice daily equal doses. Dosages adjusted achieve target CsA concentrations. The...

This study aims to determine the effect of grapefruit juice (GJ) on microemulsion cyclosporine (CsA) in 11 African American subjects, and it was compared those Caucasian subjects. Each subject received two oral doses CsA with water (W) or GJ as well IV CsA. Regardless race, significantly increased peak concentration (C max ) area under time‐curve (AUC) CsA; however, magnitude effects different between subjects (p = 0.0003). by 39% while difference only 8% > 0.05). also AUC 60%, that 44%...

To determine the relationship between C3435T mutation in exon 26 of human multidrug resistant 1 (MDR1) gene and cyclosporine pharmacokinetic parameters among healthy volunteers, oral study was performed for 14 subjects. Blood concentrations were measured by HPLC. Concentration-time data analyzed a noncompartmental method using WinNonLin, blood samples genotyped polymorphism MDR1 PCR restriction digest. Each parameter compared Mann-Whitney U test according to his or her P-gp genotype. There...

Besides general complications of immunosuppression such as increased susceptibility to opportunistic infections or malignancy, individual immunosuppressive agents are associated with specific side effects. Nephrotoxicity is the major effect cyclosporine (CsA). Various attempts have been made minimize this toxicity, monitoring drug blood levels, modifying protocol, and coadministering other agents. Other effects caused by CsA hepatotoxicity, hyperkalemia, hypertension, tremor, gum overgrowth,...

Pharmacokinetic studies of intravenous and oral cyclosporine (cyclosporin) were performed in 22 healthy African American (n = 11) white volunteers. Blood concentrations measured by high performance liquid chromatography. Concentration versus time data analyzed noncompartmental models, statistical analyses ANOVA. The clearance was 4.3 ± 0.9 mL/min/kg 13.5 4.5 mL/min/kg, respectively, Americans 3.7 0.5 9.6 the volunteers (P .0001). There a significant race gender interaction .038)....

To determine the relationship between CYP3A5 polymorphism and cyclosporine pharmacokinetic parameters among healthy volunteers, an oral (CsA) study was performed in 16 subjects. Blood CsA concentrations were measured by high-performance liquid chromatography. Concentration-versus-time data analyzed a noncompartmental method using WinNonLin, blood samples genotyped for polymerase chain reaction pyrosequencing. dichotomized compared 1-way ANOVA test according to CYP3A5*3C genotype. There 6...

New-onset diabetes after transplantation (NODAT) is one of the major complications and associated with reduced overall patient graft survival. The objective this study was to determine genetic clinical risk factors for NODAT in Hispanic kidney transplant recipients.Hispanic allograft recipients without evidence preexisting who developed (n=133) were studied using no as a control group (n=170). defined fasting glucose levels ≥126 mg/dL on two or more occasions patients taking any insulin oral...

This study was conducted to determine the effect of grapefruit juice on pharmacokinetics microemulsion cyclosporine and its major metabolites, M1 M17, in 12 healthy volunteers. Each subject received two oral doses with water or juice. also intravenous a separate occasion. Blood samples were collected for assay cyclosporine, M1, M17 during 24‐hour period, analyzed by high‐performace liquid chromatography method. Compared water, administration significantly increased peak concentration (C max...

To determine the relationship between CYP3A4*1B polymorphism and cyclosporine pharmacokinetic parameters among healthy volunteers, oral study was performed in 14 subjects. Blood concentrations were measured by a high performance liquid chromatography. Concentration-time data analyzed non-compartmental method using WinNonLin, blood samples genotyped for 5'-promotor region polymerase chain reaction restriction digest. Each parameter compared one-way ANOVA test according to his or her genotype....

Transcription factors of the nuclear factor activated T cells (NFAT) family regulate both immune activation and insulin production. Calcineurin inhibitors (CNIs) target NFAT activation. Hence, CNIs not only prevent organ transplant rejection but also contribute to development new-onset diabetes after transplantation (NODAT). Given individual variation in susceptibility NODAT, we hypothesized that polymorphisms cytoplasmic (NFATc)4 gene, which is expressed pancreatic islets, may be associated...

A study was conducted to examine the effect of grapefruit juice on disposition quinidine sulfate and changes QT intervals after oral administration twelve healthy male volunteers. Participants received two doses tablets (400 mg) with 240 mL water or juice, each separated by a 1‐week washout period. Plasma samples for analysis its major metabolite, 3‐hydroxyquinidine, were collected 24‐hour period analyzed high‐performance liquid chromatography method. For pharmacodynamic data,...

This study was designed to establish a simple and reliable assay method that could be routinely used in the clinical laboratory setting using liquid extraction high-performance chromatography (HPLC). In addition, case of potential interaction grapefruit juice with sildenafil citrate is presented. The peaks (measured as salt) internal standard were identified an ultraviolet detector at 230 nm detection limit 10 ng/mL. single elderly male patient, increased Cmax by 42% (1067.7 ng/mL 1517.0...

This study aims to assess the predictability of individual tacrolimus (FK) concentrations at different time points for area under curve (AUC) and find best sampling abbreviated AUC predict total body exposure FK. A 23 FK blood concentration versus profiles (11 samples per 12 hours) was studied in stable patients with liver transplants steady state. Each calculated by trapezoidal rule, relationship between or determined linear regression. The trough from morning dose better than evening (r2 =...

This study investigated the effect of grapefruit juice on cyclosporine A (CsA) bioavailability in 10 renal transplant patients. Under CsA steady state conditions, patients were randomly administered their usual dose with either 8 ounces or water. Using a crossover design, 12-hr pharmacokinetic was then conducted. Grapefruit increased area under concentration versus time curve(4281±1497 ng·hr/ml [grapefruit juice] vs. 3415±1288 [water], P=0.029) and trough(244±214 ng/ml 132±56...

A 12-week, randomized, double-blind, multicenter pharmacokinetic study was conducted to compare the clinical safety and tolerability of cyclosporine capsules oral solution for microemulsion in 101 primary renal transplant recipients. Cyclosporine emulsion has more complete absorption improved bioavailability compared with cyclosporine, dosing both formulations adjusted achieve comparable whole-blood trough levels. Mean serum creatinine values were higher group at baseline, 8, 12 weeks...

The aim of this study was to determine the relationship between single nucleotide polymorphisms in multidrug resistance protein 2 (MRP2) and uridine diphosphate glucuronosyltransferase (UGT) 2B7 severity gastrointestinal (GI) symptoms patients receiving mycophenolic acid (MPA). A total 67 renal transplant recipients taking MPA derivatives were included study. Genotypes for MRP2 C-24 T UGT2B7 C802 determined. incidence GI assessed using validated Gastrointestinal Symptom Rating Scale (GSRS)...

The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 recipients biopsied for dysfunction with test results available: 23 patients diffusely positive C4d (C4d+), 25 focally C4d, negative (C4d−). performed C1q IgG subclass testing in our DSA+ C4d+ patient group. Graft outcomes were determined the All had an average of 12,500 MFI (cumulative MFI). C4d−...

The aim of this study was to characterize the circadian variation oral tacrolimus disposition in 8 stable liver allograft recipients. In steady state, a total 23 blood samples taken before and after administration during 24-hr period pharmacokinetic parameters were compared. area under curve (AUC) morning dose significantly larger than evening (211+/-43 ng x hr/ml [morning] vs. 179+/-45 [evening], P=0.02). time peak (Tmax) shorter (1.6+/-0.7 hr 2.9+/-0.6 P=0.002). (Cmax) higher (32.2+/-10.2...

A 39‐year‐old woman was evaluated for possible liver transplantation due to rapidly developing hepatic failure 4 weeks after initiation of oral minocycline 100 mg twice a day the treatment acne. The patient developed maculopapular rash, malaise, fever, nausea, and vomiting 2 prior admission hospital. On admission, her symptoms progressed characterized by rising enzyme levels, worsening encephalopathy, coagulopathy. Viral hepatitis serologies blood cultures were all negative. After intensive...

BK virus nephropathy is one of the most common viral infections that affect up to 10% renal transplant recipients (RTRs), causing allograft dysfunction and graft loss. Interferon-gamma (IFN-γ) gene polymorphisms have been associated with parvovirus B19, hepatitis C virus, HIV-1/AIDS infection, cytomegalovirus viremia, disease. IFN-γ known potent inhibitory effects on expression, both at level transcription translation.It was investigated whether are BKV infection. Genotyping four...

Abstract Background Cytomegalovirus ( CMV ) is the most common cause of viral infection, causing morbidity and mortality among renal transplant recipients RTR s). Cytokines such as tumor necrosis factor‐alpha TNF ‐α), interleukin‐10 IL ‐10), interferon‐gamma IFN ‐γ) have been shown to possess antiviral properties, their polymorphisms are associated with disease outcome. The aim was investigate association gene in ‐10, ‐γ, ‐α infection s. Methods ‐10 −1082 A>G, −592 A>C; −308 A>G; ‐γ...

Abstract Background BK virus nephropathy (BKVN) is a major complication in kidney transplant patients. This study aimed to investigate the efficacy of intravenous immunoglobulin (IVIG) therapy against persistent BKVN and evaluate association between Fc gamma receptor (FcγR) single nucleotide polymorphisms (SNPs). Methods A total 86 patients out 279 recipients with were investigated single‐center retrospective study. The majority Hispanic Asian (69.8% 17.4%). Patients treated adjunctive IVIG...

The neural network (NN) is a technique using an artificial intelligent concept in predicting outcomes by various input variables. Tacrolimus pharmacokinetics has wide inter- and intra-subject variability it often difficult to predict its blood concentrations dose alone. objectives of this study are select the clinically significant variables concentration tacrolimus liver transplant patients NN combined with genetic algorithm (GA). A total thirty-two adult from University Iowa Hospitals...