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This large, multicenter, prospective and randomized study shows no difference in the incidence of posttransplantation diabetes mellitus but higher incidence of acute rejection with a steroid avoidance versus a steroid sparing regimen in kidney transplant recipients receiving basiliximab, prolonged-release tacrolimus and mycophenolate.

Micafungin is an echinocandin with potent activity against a broad range of fungal species, including Candidaspecies. The pharmacokinetic and safety profiles of micafungin have been evaluated in individuals with mild-to-moderate hepatic dysfunction, but not in individuals with severe hepatic dysfunction. Therefore, the present study assessed the pharmacokinetics and safety of a single 100 mg dose of micafungin in healthy subjects (n= 8) and subjects with severe hepatic dysfunction (n= 8). Mean maximum plasma concentration of micafungin and mean area under the plasma micafungin concentration–time curve extrapolated to infinity were lower in subjects with severe hepatic dysfunction (7.3 ± 2.4 µg/mL and 100.1 ± 34.5 h·μg/mL, respectively) than in subjects with normal hepatic function (10.3 ± 2.5 µg/mL and 142.4 ± 28.9 h·μg/mL, respectively). Mean clearance was higher in subjects with severe hepatic dysfunction (1,098 ± 347 mL/h) than in subjects with normal hepatic function (728 ± 149 mL/h). Concentrations of albumin in subjects with severe hepatic dysfunction were lower. Assessments of micafungin plasma protein binding suggested that the higher clearance in subjects with severe hepatic dysfunction may be due to higher unbound concentrations. However, the magnitude of the differences was not considered clinically meaningful and is comparable with exposures reported elsewhere for a 100-mg dose in patients treated for invasive candidiasis. Thus, dose adjustment in subjects with severe hepatic dysfunction is not warranted. Micafungin was well tolerated in all subjects throughout the study.

Tacrolimus has originally been registered as a twice-daily formulation (Prograf, Tac BID), although a once-daily formulation (Advagraf, Tac QD) is also available. A reduced intrapatient variability of Tac Cmin, a surrogate marker for 24-hour drug exposure (AUC0–24), has been suggested. The variability of AUC0–24has never been studied prospectively yet. The purpose of this study was to investigate the change in intrapatient variability of Tac AUC0–24after converting from Tac BID to Tac QD.

Tacrolimus is a well-established immunosuppressive agent for the treatment and prevention of solid organ graft rejection. It is available as an immediate-release, twice-daily formulation (Tacrolimus BID) and a prolonged-release, once-daily formulation (Tacrolimus QD). In a previous study of the pharmacokinetics (PK) of these formulations, mean systemic exposure area under the curve from 0 to 24 hours (AUC0–24) of tacrolimus on day 1 was approximately 30 lower for Tacrolimus QD than for Tacrolimus BID; by day 14, systemic exposure was similar; however, the mean dose of Tacrolimus QD was higher to achieve similar systemic exposure as Tacrolimus BID.

A prolonged-release formulation of tacrolimus for once-daily administration (Tacrolimus QD) has been developed to offer potential improvements in patient adherence. This study compared the pharmacokinetics (PK) of tacrolimus in stable kidney transplant recipients before and after conversion from twice-daily tacrolimus (Tacrolimus BID) to Tacrolimus QD.

The once-daily formulation of tacrolimus has been reported to exhibit the same efficacy and safety profile as compared with the immediate-release form administered twice daily. However, as a result of differences in their pharmacokinetic (PK) profile, the PK models or Bayesian estimators (MAP-BE) previously developed for the immediate-release formulation cannot be used for the new once-daily formulation. Using the PK information obtained from a Phase II trial, the aim of this study was to explore the feasibility of developing a PK model and a MAP-BE able to estimate, on the basis of a routinely applicable limited sampling strategy, tacrolimus individual PK parameters and AUC0-24hin de novo renal transplant patients given the once-daily formulation.

Background:An association between hepatitis C virus and (post-transplant) diabetes mellitus has been reported. Methods:We report a patient on tacrolimus-based immunosuppression who developed an episode of post-transplant diabetes mellitus (PTDM) 2 years after renal transplantation, after contracting a hepatitis C infection. Her glucose metabolism was evaluated regularly by intravenous glucose tolerance tests before and after the PTDM episode. Results:Before contracting hepatitis C, the patient's insulin resistance and insulin secretion were normal. After contracting hepatitis C, tacrolimus exposure increased, insulin resistance increased, and insulin secretion decreased markedly. Despite low tacrolimus exposure in the last 4 years, glucose metabolism did not recover completely. Although PTDM resolved and insulin resistance normalized, pancreatic β cell secretion remained impaired by approximately 50% compared with the period before hepatitis C infection. Conclusion:After an initial increase in insulin resistance, insulin secretion decreased markedly in a patient who contracted hepatitis C 12 to 22 months after renal transplantation. This change resulted in an episode of PTDM. Increased tacrolimus exposure secondary to reduced cytochrome P-450 metabolism as a result of impaired hepatocellular function at the time of the development of PTDM seems a likely explanation for the marked decrease in insulin secretion. Viral toxicity to the β cell might be an additional explanation. The latter might be suspected from several reports about an association between diabetes mellitus and hepatitis C in patients who do not use drugs that interfere with glucose metabolism. © 2002 by the National Kidney Foundation, Inc.

Although micafungin pharmacokinetic values were comparable between younger (<5 years) and older children (≥5 years) with candidemia and invasive candidiasis, younger children had a lower peak plasma micafungin concentration, lower micafungin exposure and larger micafungin clearance. Half-life remained unchanged with repeated dosing. Metabolite plasma concentrations remained low in older children; however, metabolite M-5 concentrations were higher in younger children.