Cyclosporine monitoring in the early post-transplant period in pediatric liver transplant recipients.

UNLABELLED: Monitoring of CsA blood levels two h post-dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post-transplant until they were able to ingest oral medication. The study was continued until one yr of post-transplant follow-up. Eight h pharmacokinetic profiles were performed on days one, three, and five post-transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC(0-8 h). Intravenous administration of CsA was required in 55% of patients. The biopsy-confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. CONCLUSIONS: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post-transplant period.

Plasma trough levels of mycophenolic acid do not correlate with efficacy and safety of mycophenolate mofetil in psoriasis.

BACKGROUND: Mycophenolate mofetil (MMF) has been shown to be effective for systemic treatment of psoriasis. MMF is the prodrug of mycophenolic acid (MPA), the pharmacologically active compound. The measurement of plasma MPA levels could be useful for optimizing therapeutic management using MMF. OBJECTIVES: To investigate whether plasma trough levels of MPA correlate with the efficacy and safety of oral MMF in the treatment of patients with psoriasis. METHODS: Six patients (four women and two men, mean age 58 years) with severe chronic plaque-type psoriasis were treated with oral MMF 1 g twice daily. The Psoriasis Area and Severity Index (PASI), routine laboratory examinations and plasma MPA trough levels, measured by an enzyme-multiplied immunoassay (EMIT), were determined at 2 weeks and 1, 3, 5 and 7 months. RESULTS: All the patients experienced a marked improvement within the first 15 days and continued to do so for 5-7 months. Two patients achieved complete remission. MMF was well tolerated. MPA levels showed a wide intra- and interindividual variability. There was no significant correlation between MPA trough levels and the reduction of the PASI or the presence of adverse effects, but a good correlation with therapeutic compliance. CONCLUSIONS: The monitoring of MPA trough levels with EMIT appears to be a poor predictor of efficacy or toxicity. In contrast, it is a useful tool to evaluate the degree of therapeutic compliance.

[Changes in the flow of the stable renal graft following cyclosporin administration]. / Cambios en el flujo del injerto renal estable tras la administración de ciclosporina.

To evaluate whether oral CyA may produce changes in the renal vascular bed of the graft, a prospective study was made in 16 children with kidney transplant and normal renal function. A exam with echo-Doppler was realized pre and post two hour after CyA was administered. The doses of CyA was 6.1 +/- 2.7 mg/kg/days (3 doses). The results show that CyA produced in the children with kidney transplant an increase of vascular resistance (renal and interlobar) and a decrease transient of urinary flow. The finding changes in relation to time of administration of the CyA.