| Title | Age-Related Variability of Mycophenolate Mofetil Exposure in Stable Pediatric Liver Transplant Recipients and Influences of Donor Characteristics. | | Author(s) | Parant F, Rivet C, Boulieu R, Gagnieu MC, Dumortier J, Boillot O, Lachaux A | | Institution | From the *Hospices Civils de Lyon, Hôpital Edouard Herriot, Pharmacologie Spécialisée, Fédération de Biochimie, Lyon, France; daggerHospices Civils de Lyon, Hôpital Femme Mère Enfant, Service de Pédiatrie, Bron, France; double daggerUniversité de Lyon, Université Lyon1, ISPB, Département de Pharmacie Clinique, de Pharmacocinétique et d'Evaluation du Médicament, INSERM ERI 22 Lyon, France; and section signHospices Civils de Lyon, Hôpital Edouard Herriot, Fédération de Spécialités Digestives, Lyon, France. | | Source | Ther Drug Monit 2009 Oct 29. | | Abstract | Despite the increasing use of mycophenolate mofetil (MMF) in pediatric liver transplantation recipients, data on MMF pharmacokinetics in this population are relatively scattered. This pilot study was performed to explore whether recipient age-related factors, in conjunction with donor factors, can explain variability in mycophenolic acid (MPA) exposure. Thirty-four MPA pharmacokinetic profiles were performed in 20 stable pediatric liver transplantation recipients (median age, 12 years; range, 1-18 years; median delay after liver transplant, 88 months; range, 3-179 months). Ten children were converted to MMF; the others received MMF as a primary immunosuppressive regimen. MMF was used in combination with tacrolimus. Plasma MPA concentrations were analyzed samples collected at 0, 1, 3, and 6 hours after MMF administration using the enzyme multiplied immunotechnique immunoassay. The median MMF dose was 431 mg/m per day (range, 189-833 mg/m per day) leading to a median estimated MPA-AUC0-12h of 27 mg/h/L (range, 17-79 mg/h/L). Dose-normalized MPA-AUCs were characterized by high interpatient variability. Young children receiving a liver from a pediatric donor had lower MPA exposure compared with those receiving liver from an adult donor. No correlation was seen between MPA-C0 and MPA-AUC0-6h in infants, whereas this correlation was significant but moderate in older children. The interpatient variability of MPA exposure observed with this pilot study is an argument for developing therapeutic drug monitoring-based dose adaptation strategies in pediatric liver transplantation recipients. A marked MPA underexposure was observed among young children receiving livers from pediatric donors, indicating that higher doses (mg/m of body surface area) might be required to reach the same MPA exposure as in adolescents. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19881404 |
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