Monitoring of Tacrolimus as Rescue Therapy in Pediatric Liver Transplantation

Abstract

The introduction of tacrolimus as rescue therapy represents a significant advance in the prevention of late graft failure and second liver transplantation. The authors report the blood level monitoring of tacrolimus as a rescue therapy in 21 children who underwent liver transplantation, and they report the dose-concentration relationship in the presence or absence of hepatitis C virus (HCV) in these patients. This was a retrospective study conducted from May 1993 to January 1997. Indication for the conversion from cyclosporine (CsA) to tacrolimus were acute rejection (62%), chronic rejection (33%), and CsA toxicity (5%). Mean daily dose in the first month was 0.32 mg/kg, whereas at the end of the follow-up period it was 0.14 mg/kg. Tacrolimus mean whole blood concentration levels were between 7.1 ng/ml and 9.4 ng/ml, without significant differences over time. Mean daily doses in HCV+ and HCV- patients were 0.08 and 0.24 mg/kg, respectively (p < 0.01), and mean concentrations were 8.3 and 8.4 ng/ml (NS). HCV+ children required a mean dose three times lower than the dose used in HCV- children to obtain the same tacrolimus trough blood level. Therefore, doses in HCV+ children must be decreased to achieve levels within the therapeutic range.

Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patients

“…In the adult population, 35% were positive for hepatitis C, whereas only 12% of the pediatric population were hepatitis C positive. As reported by previous investigators, the tacrolimus dose for hepatitis C‐positive subjects was far lower than that for the rest of the population, while their tacrolimus trough concentrations were consistent with hepatitis C‐negative subjects (17). The proportion of males and females in each population was the same.…”

Alendronate therapy in cyclosporine‐induced alveolar bone loss in rats

“…In humans, the incidence, as well as the progression, of cyclosporine A‐induced bone loss seems to be variable. Although there is some controversy in the literature, there is accumulating evidence that in humans cyclosporine A has a negative impact on bone metabolism (3,5,30,34–39). Discrepancies in the data reported may be caused by differences in drug dosage, gender and age among the individuals included in the studies.…”

“…Moreno et al . (37) related that alendronate in vitro does not affect the viability, proliferation and mineral deposit capacity of human osteoblasts.…”

A Novel Approach to Managing Variation: Outpatient Therapeutic Monitoring of Calcineurin Inhibitor Blood Levels in Liver Transplant Recipients

“…We obtained consensus on target levels for CNIs as a function of time since transplantation. [31][32][33][34] The process involved transplant surgeons, hepatologists, nurse coordinators, and pharmacists who make up the clinical arm of the interdisciplinary liver transplantation care team at Cincinnati Children's Hospital. The target range for tacrolimus was 8 to 12 ng/mL during the period of 3 to 6 months after transplantation, 6 to 10 ng/mL 6 months to 12 months after transplantation, and 3 to 8 ng/mL >12 months after transplantation.…”