Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy.

Aims: 6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharmacogenetic polymorphisms affecting thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) on 6-MP metabolism and response.

Population pharmacokinetics and pharmacogenetics of mycophenolic acid following administration of mycophenolate mofetil in de novo pediatric renal-transplant patients.

The objective was to develop a population pharmacokinetic-pharmacogenetic model of mycophenolic acid following administration of mycophenolate mofetil (MMF) in de novo pediatric renal-transplant patients and identify factors that explain variability. The pharmacokinetic samples were collected from 89 de novo pediatric renal-transplant patients treated with MMF and studied during the first 60 postoperative days. All patients were genotyped for UGT1A8-A9, UGT2B7, and ABCC2.

mRNA expression of MDR1 and major metabolising enzymes in human fetal tissues.

Metabolising enzymes and transport proteins are largely expressed in human tissues. They have major impact on drug disposition and effects. We studied mRNA expression of phase I and II metabolising enzymes and transporters in fetal tissues at different development stages.

Comparison of high-performance liquid chromatography and enzyme-multiplied immunoassay technique to monitor mycophenolic acid in paediatric renal recipients.

Therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) is recommended to guide immunosuppression. High-performance liquid chromatography with ultraviolet (HPLC-UV) or the enzyme-multiplied immunoassay technique (EMIT), used to measure mycophenolic acid (MPA) were compared in an exclusive paediatric renal transplant population. Twenty patients were included as part of the pharmacokinetics study of MMF, and 88 additional samples were drawn for TDM.