Pharmacokinetics and Therapeutic Target Attainment of Meropenem in Pediatric Post-Liver Transplant Patients: Extended vs Intermittent Infusion.

Purpose: The aim of this study is to characterize the concentration-time profile, pharmacokinetics parameters, and therapeutic target attainment of meropenem in pediatric post-liver transplant patients according to the duration of infusion.

Methods: This is a prospective cohort of pediatric transplant recipients with preserved renal function receiving meropenem 40 mg/kg every 8 hours. The patients were stratified into 2 groups based on infusion duration: G1 (15 minutes of intermittent infusion) and G1 (3 hours of extended infusion).

Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?

Background: In regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success.

Objective: Evaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA.

Methods: The measurement was performed at least 7-days after initiation of therapy.

A rare association between factor H deficiency and lupus: Case report and experimental treatment with curcumin.

Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. FH deficiency is a rare condition that causes unregulated C3 consumption, leading to an increased susceptibility to infections and glomerulopathies. Our previous studies have demonstrated a FH deficient patient carrying a c.

Thalidomide measurement in plasma and dried plasma spot by SPE combined with UHPLC-MS/MS for therapeutic drug monitoring.

To validate an SPE-ultra-HPLC-MS/MS method for thalidomide (THD) measurement in dried plasma spot (DPS). Extraction included acetonitrile/water clean-up and online SPE. The LOD, LLOQ, linearity, precision, accuracy, recovery, matrix effect, process efficiency, carryover, stability, drug interference and dilution integrity were assessed.

UHPLC-MS/MS Method for Determination of Hydroxychloroquine and Its Main Metabolites in Oral Fluid and Whole Blood for Therapeutic Drug Monitoring.

Background: Hydroxychloroquine (HCQ) blood levels are used to monitor efficacy, safety, and patient adherence during treatment. Oral fluid has emerged as an alternative noninvasive, easily accessible, and low-complexity matrix for drug monitoring. However, there is no analytical method to measure HCQ in oral fluid.

Longitudinal Pharmacokinetics of Mycophenolic Acid in Elderly Renal Transplant Recipients Compared to a Younger Control Group: Data from the nEverOld Trial.

Background And Objectives: Elderly patients are increasingly likely to be recipients of transplants. However, the pharmacokinetics of mycophenolic acid (MPA) in this population are yet to be studied in detail. The objective of this study was to assess whether there were differences in MPA pharmacokinetic parameter values between elderly recipients and younger-adult recipients during the 6 months immediately following renal transplantation.

Development of an Abbreviated Mycophenolic Acid Area Under the Time-Concentration Curve for Renal Transplant Patients Under Enteric-Coated Mycophenolate Sodium: A Comparison With Critical Analysis of Available Equations.

Background: Enteric-coated mycophenolate sodium is frequently used in renal transplantation. The pharmacokinetic profile of mycophenolic acid (MPA) shows a broad range of time-to-maximum concentration (Tmax) that limits the use of a single MPA concentration to calculate the area under the time-concentration curve (AUC). For both research and clinical MPA monitoring, measuring a complete AUC is troublesome to the center and patients.

UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+ and B CD19+ lymphocytes.

Monitoring tacrolimus (Tac) exposure in cell matrices enriched with lymphocytes can improve Tac therapeutic drug monitoring (TDM) in solid organ transplant recipients. An UPLC-MS/MS based assay for Tac quantification in peripheral blood T CD4+ and B CD19+ lymphocytes was developed. Peripheral blood mononuclear cells (PBMC) were obtained by density gradient centrifugation and highly purified (purity >90%) T CD4+ and B CD19+ cell suspensions were acquired by magnetic negative selection from whole blood of 6 healthy volunteers.

Longitudinal Pharmacokinetics of Everolimus When Combined With Low-level of Tacrolimus in Elderly Renal Transplant Recipients.

Background: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients.

Methods: We studied 12-hour everolimus (EVL) PK in 16 elderly renal transplant recipients (all whites; 10 men; mean age, 64 ± 2 years (61-71 years), in 4 separate timepoints (at 7, 30, 60, and 150 days) after EVL introduction, corresponding to a mean postrenal transplantation day: PK1 (43 ± 4 days), PK2 (65 ± 7 days), PK3 (106 ± 17 days), and PK4 (206 ± 40 days). Patients received EVL (target trough level (Ctrough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target Ctrough, 2-5 ng/mL).

Longitudinal Pharmacokinetics of Tacrolimus in Elderly Compared With Younger Recipients in the First 6 Months After Renal Transplantation.

Background: Elderly (Eld) (≥60 years) recipients are receiving renal transplants more frequently. The pharmacokinetics (PK) studies of immunosuppressive drugs in healthy volunteers, rarely, include old patients.

Methods: We studied 208 12-hour tacrolimus (TAC) PK (0, 20, 40, 60, 90, 120, 180, 240, 360, 480, 600, 720 min) in 44 Eld (65 ± 3 years) and compared the results with 31 younger controls (Ctrl) (35 ± 6 years) recipients, taking oral TAC/mycophenolate sodium (MPS)/prednisone, at 4 different timepoints: PK1 (8 ± 2 days; n = 72), PK2 (31 ± 4 days; n = 61), PK3 (63 ± 6 days; n = 44), and PK4 (185 ± 10 days; n = 31).

Diminished mycophenolic acid exposure caused by omeprazole may be clinically relevant in the first week posttransplantation.

Background: Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant.

Methods: We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC)(0-12h)] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials.

The need of mycophenolic acid monitoring in long-term renal transplants.

Background: There is little information regarding the 12-h mycophenolic acid (MPA) pharmacokinetics (PK), a way to monitor the drug and the need of frequent monitoring, in stable patients.

Methods: A cohort of 35 adults, under long-term mycophenolate mofetil (MMF) therapy plus cyclosporin A (n = 12), TACimus (n = 12) or MMF only (n = 11); all with prednisone had a 12-h MPA-PK performed to ascertain the percentage of them within a defined therapeutic window. In 13 other patients, two PK studies undergone 1 wk apart were performed to evaluate the need for frequent measurements.

Bioequivalence of a new cyclosporine a formulation to Neoral.

New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.

Mycophenolic acid pharmacokinetics in stable pediatric renal transplantation.

Mycophenolate mofetil (MMF) is given to children in fixed doses based either on body weight or body surface area. There are data indicating mycophenolic acid (MPA) blood levels should be monitored in the early period of transplantation. However, there is little information regarding MPA pharmacokinetics (PK) in stable pediatric recipients.

Impact of cyclosporin A pharmacokinetics on the presence of side effects in pediatric renal transplantation.

Cyclosporin A (CsA) is a potent immunosuppressant that has many side effects, including hypertrichosis, gingival hyperplasia, and tremor. To evaluate whether there is a relationship between the CsA-pharmacokinetics (PK) and these side effects, their presence and intensity were observed in 46 renal transplanted children/adolescents during two regular visits, and the occurrence of the side effects was correlated with CsA-PK. CsA doses had been unchanged for at least 6 mo.