Miocardiopatía hipertrófica en un recién nacido pretérmino con madre trasplantada renal / Hypertrophic cardiomyopathy in preterm newborn with kidney transplanted mother

La miocardiopatía hipertrófica en el recién nacido es una entidad poco frecuente y de etiología heterogénea. Se han descrito formas transitorias en hijos de madres con diabetes gestacional y en recién nacidos pretérminos expuestos a corticoides tanto prenatal como posnatalmente. Se presenta un caso de un recién nacido pretérmino, hijo de madre trasplantada renal al que se le detectó una miocardiopatía hipertrófica y que había estado expuesto prenatalmente a corticoides y tacrolimus que recibía la madre como tratamiento inmunosupresor. Ambos fármacos cruzan la barrera placentaria y, al llegar al feto, podrían haber favorecido su desarrollo. La miocardiopatía hipertrófica puede ser un efecto secundario poco común del tratamiento con tacrolimus en adultos y niños, y es reversible al retirarlo. En nuestro conocimiento, es el primer caso publicado de miocardiopatía hipertrófica transitoria tras la exposición fetal tanto a corticoides como a tacrolimus en un hijo de madre trasplantada renal.

Hypertrophic cardiomyopathy in the newborn is a rare entity with heterogeneous etiology. Transient forms have been described in children of mothers with gestational diabetes and in preterm infants exposed both to prenatal and postnatal corticosteroids. We report a case of a preterm infant son of a mother who received renal transplant in whom hypertrophic cardiomyopathy was detected. He had been prenatally exposed to corticosteroids and tacrolimus that received the mother as immunosuppressive therapy. Both drugs cross the placental barrier and, on reaching the fetus, could have favored its development. Hypertrophic cardiomyopathy may be an uncommon side effect of treatment with tacrolimus in adults and children and it is reversible upon withdrawal. To our knowledge, it is the first published case of transient hypertrophic cardiomyopathy after fetal exposure to both corticosteroids and tacrolimus in the son of a renal transplanted mother.

Cytochrome P450 3A4[asterisk]1B as pharmacogenomic predictor of tacrolimus pharmacokinetics and clinical outcome in the liver transplant recipients

Tacrolimus is a macrolide immunosuppressant used for prevention of allograft rejection in organ transplantation and metabolized in the liver and intestine by cytochrome P450 3A4 [CYP3A4] enzyme. A single nucleotide polymorphism [SNP] in the CYP3A4 promoter region has been identified. It has been shown that the presence of CYP3A4[asterisk]1B allele [variant GG] is associated with a reduced catalytic activity of CYP3A4 in vivo. The aim of this study was to determine the role of CYP3A4[asterisk]1B on tacrolimus dosing and clinical outcome in liver transplant recipients. Forty-eight liver transplant recipients were stratified according to the genotype. There were 32 wild-type [AA] patients and 5 homozygous variant [GG] and 11 [AG] heterozygous. Tacrolimus doses and trough concentrations as well as phenotypic data were collected in the first 10 days of the transplant. The tacrolimus concentration was significantly higher in the wild [AA] group as compared to homozygous variant [GG] and heterozygous [AG] patients. Homozygous variant [GG] group had significantly lower dose requirements. However, no significant difference was observed in the concentration/dose ratio between all groups. Based on our results, it may be concluded that CYP3A4[asterisk]1B of recipient is an important factor influencing pharmacokinetic of tacrolimus, as patients with CYP3A4[asterisk]1B polymorphism may require lower tacrolimus doses to maintain therapeutic levels. The dose reduction may not affect clinical outcomes after liver transplant

Determination of tacrolimus in pharmaceutical formulations by validated spectrophotometric methods

Two simple, rapid and sensitive spectrophotometric methods were developed for the determination of tacrolimus in pharmaceutical dosage forms. The methods, based on the sulphuric acid reaction and on thei odine charge-transfer reaction, gave absorption peaksat 295 nm and 365 nm, respectively. The calibrationcurves were linear in the concentration range of 30-55 miug mL-1 for the sulphuric acid method (r² equal 0.9999)and 5-10 miug mL-1 (r² equal 0.9999) for the charge-transfer method. The specificity was assessed, showing that there was no interference from the excipients. The accuracyof both of the methods was higher than 99.44%, witha bias lower than 2%, and high precision was also demonstrated. The limits of quantitation for the two methods were 30 miug mL-1 and 5 miug mL-1. The proposed methods were applied to the determination of tacrolimusin capsule dosage forms, and the results compared statistically with the validated reversed-phase liquid chromatography (RP-LC) method, showing significant correlation (p smaller that 0.05) and demonstrating either method to be an excellent alternative to LC. The application of these simple methods to routine quality control analysisof pharmaceuticals could contribute to their safety and therapeutic efficacy.

Co-interferências da farmacocinética dos inibidores de calcineurina em associação com micofenolato mofetil em pacientes transplantados renais / Interference of calcineurin inhibitors on the pharmakocinetics of mycophenolic acid in renal transplantation

O ácido micofenólico (MPA) é o metabólito ativo do micofenolato mofetil (MMF), um imunossupressor seletivo para linfócitos amplamente utilizado em transplantes. A exposição ao MPA na fase inicial pós-transplante renal está associada com menor incidência de rejeição aguda e com maior sobrevida do enxerto / Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF), a selective lymphocyte anti-proliferative drug. It has been demonstrated that early adequate exposure to MPA is associated with less acute rejection and better long-term outcome in kidney transplantation. To the present, the recommended therapeutic range for MPA is an area under the concentration-time curve...