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Pharmacokinetic and pharmacogenetic analysis of tacrolimus in pediatric liver transplant patients in the early post-liver transplantation period
Digestive and Liver Disease 46 (2014) e71–e84
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Abstracts of the XXI National SIGENP Congress: Oral Communications
PHARMACOKINETIC AND PHARMACOGENETIC ANALYSIS OF TACROLIMUS IN PEDIATRIC LIVER TRANSPLANT PATIENTS IN THE EARLY POST-LIVER TRANSPLANTATION PERIOD Pier Luigi Calvo 1,∗ , Michele Pinon 1 , Roberto Canaparo 2 , Antonio D’Avolio 3 , Andrea Brunati 4 , Debora Pensi 3 , Amedeo De Nicolò 3 , Giulia Carbonaro 4 , Alessia Cerrina 4 , Antonello Nonnato 5 , Renato Romagnoli 4 , Cristiana Barbera 1 , Mauro Salizzoni 4
The other polymorphisms and the transplant type did not show any influence on tacrolimus blood levels. Conclusions: Hepatic metabolism of donor has more important consequences on tacrolimus pharmacokinetics than extrahepatic metabolism of recipients immediately in the early pot-liver transplantation period. Pharmacogenetic analysis of CYP3A5 in the donor before transplantation, particularly in children less than 8 years, could contribute to determine the appropriate initial dosage of tacrolimus. http://dx.doi.org/10.1016/j.dld.2014.07.021
1
Department of Pediatric Gastroenterology and Hepatology, Regina Margherita Children’s Hospital, Azienda Ospedaliera Città della Salute e della Scienza, University of Turin, Turin, Italy 2 Department of Drug Science and Technology, University of Turin, Turin, Italy 3 Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy 4 Liver Transplantation Center, Azienda Ospedaliera Città della Salute e della Scienza, University of Turin, Turin, Italy 5 Laboratorio Baldi Riberi, Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy Objective: Tacrolimus is characterized by a restricted therapeutic index, a high inter- and intra-individual pharmacokinetic variability and a series of severe adverse effects. It is a substrate of cytochrome p-450 (CYP) 3A enzyme and of the drug transporter ABCB1. Methods: Tacrolimus doses (mg/kg/die), C0 blood levels and dose-adjusted C0 concentration (C/D/Kg) were determined every day during the first 2 weeks of the post-liver transplantation period. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A*3, CYP3A4*22 and ABCB1 (3435C>T and 1199A>G). We evaluated the influence of these polymorphisms in both donors and recipients and other factors (patient age and sex, transplant type) on tacrolimus blood levels in a cohort of 78 pediatric liver recipients under tacrolimus-based monotherapy. Results: Tacrolimus dose requirements were significantly higher in children less than 8 years old, particularly under 2 years old, and in patients receiving a liver from CYP3A5*1/*3 allele compared to those homozygous for the *3 allele. The last difference was statistically significantly from day 1 till day 10. Female recipients tended to have higher C/D/kg, statistically significantly at day 1.
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EXTRA-HEPATIC PORTAL VEIN OBSTRUCTION IN CHILDREN: A MULTICENTRE NATIONAL STUDY Angelo Di Giorgio 1,∗ , Paola De Angelis 2 , Mara Colusso 3 , Pietro Vajro 4 , Raffaele Iorio 5 , Graziella Guariso 6 , Silvia Riva 7 , Giuseppe Maggiore 8 , Giuseppe Indolfi 9 , Maurizio Baldi 10 , Lorenzo D’Antiga 11 1 Paediatric Liver, GI and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy 2 Paediatric Surgery and Endoscopy, Ospedale Pediatrico Bambino Gesù, Roma, Italy 3 Paediatric Surgery, Ospedale Papa Giovanni XXXIII, Bergamo, Italy 4 Paediatric Department, University of Salerno, Salerno, Italy 5 Paediatric Liver, University Federico II, Napoli, Italy 6 Paediatric Department, University of Padova, Padova, Italy 7 Paediatric Transplantation, ISMETT, Palermo, Italy 8 Paediatric Department, University of Pisa, Pisa, Italy 9 Paediatric Liver, Ospedale Pediatrico Meyer, Firenze, Italy 10 Paediatric Department, Ospedale Infantile Regina Margherita, Torino, Italy 11 Paediatric Liver, GI and Transplantation, Ospedale Papa Giovanni XXXIII, Bergamo, Italy
Objective: We report features at birth, at presentation and at the last follow up of children with Extrahepatic Portal Vein Obstruction (EHPVO) in order to favour an early diagnosis and a best management of the disease. Methods: A questionnaire was sent to the Italian liver centres to collect data on demographic features, history of prematurity
Contents lists available at ScienceDirect
Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld
Abstracts of the XXI National SIGENP Congress: Oral Communications
PHARMACOKINETIC AND PHARMACOGENETIC ANALYSIS OF TACROLIMUS IN PEDIATRIC LIVER TRANSPLANT PATIENTS IN THE EARLY POST-LIVER TRANSPLANTATION PERIOD Pier Luigi Calvo 1,∗ , Michele Pinon 1 , Roberto Canaparo 2 , Antonio D’Avolio 3 , Andrea Brunati 4 , Debora Pensi 3 , Amedeo De Nicolò 3 , Giulia Carbonaro 4 , Alessia Cerrina 4 , Antonello Nonnato 5 , Renato Romagnoli 4 , Cristiana Barbera 1 , Mauro Salizzoni 4
The other polymorphisms and the transplant type did not show any influence on tacrolimus blood levels. Conclusions: Hepatic metabolism of donor has more important consequences on tacrolimus pharmacokinetics than extrahepatic metabolism of recipients immediately in the early pot-liver transplantation period. Pharmacogenetic analysis of CYP3A5 in the donor before transplantation, particularly in children less than 8 years, could contribute to determine the appropriate initial dosage of tacrolimus. http://dx.doi.org/10.1016/j.dld.2014.07.021
1
Department of Pediatric Gastroenterology and Hepatology, Regina Margherita Children’s Hospital, Azienda Ospedaliera Città della Salute e della Scienza, University of Turin, Turin, Italy 2 Department of Drug Science and Technology, University of Turin, Turin, Italy 3 Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy 4 Liver Transplantation Center, Azienda Ospedaliera Città della Salute e della Scienza, University of Turin, Turin, Italy 5 Laboratorio Baldi Riberi, Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy Objective: Tacrolimus is characterized by a restricted therapeutic index, a high inter- and intra-individual pharmacokinetic variability and a series of severe adverse effects. It is a substrate of cytochrome p-450 (CYP) 3A enzyme and of the drug transporter ABCB1. Methods: Tacrolimus doses (mg/kg/die), C0 blood levels and dose-adjusted C0 concentration (C/D/Kg) were determined every day during the first 2 weeks of the post-liver transplantation period. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A*3, CYP3A4*22 and ABCB1 (3435C>T and 1199A>G). We evaluated the influence of these polymorphisms in both donors and recipients and other factors (patient age and sex, transplant type) on tacrolimus blood levels in a cohort of 78 pediatric liver recipients under tacrolimus-based monotherapy. Results: Tacrolimus dose requirements were significantly higher in children less than 8 years old, particularly under 2 years old, and in patients receiving a liver from CYP3A5*1/*3 allele compared to those homozygous for the *3 allele. The last difference was statistically significantly from day 1 till day 10. Female recipients tended to have higher C/D/kg, statistically significantly at day 1.
1590-8658/$36.00
EXTRA-HEPATIC PORTAL VEIN OBSTRUCTION IN CHILDREN: A MULTICENTRE NATIONAL STUDY Angelo Di Giorgio 1,∗ , Paola De Angelis 2 , Mara Colusso 3 , Pietro Vajro 4 , Raffaele Iorio 5 , Graziella Guariso 6 , Silvia Riva 7 , Giuseppe Maggiore 8 , Giuseppe Indolfi 9 , Maurizio Baldi 10 , Lorenzo D’Antiga 11 1 Paediatric Liver, GI and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy 2 Paediatric Surgery and Endoscopy, Ospedale Pediatrico Bambino Gesù, Roma, Italy 3 Paediatric Surgery, Ospedale Papa Giovanni XXXIII, Bergamo, Italy 4 Paediatric Department, University of Salerno, Salerno, Italy 5 Paediatric Liver, University Federico II, Napoli, Italy 6 Paediatric Department, University of Padova, Padova, Italy 7 Paediatric Transplantation, ISMETT, Palermo, Italy 8 Paediatric Department, University of Pisa, Pisa, Italy 9 Paediatric Liver, Ospedale Pediatrico Meyer, Firenze, Italy 10 Paediatric Department, Ospedale Infantile Regina Margherita, Torino, Italy 11 Paediatric Liver, GI and Transplantation, Ospedale Papa Giovanni XXXIII, Bergamo, Italy
Objective: We report features at birth, at presentation and at the last follow up of children with Extrahepatic Portal Vein Obstruction (EHPVO) in order to favour an early diagnosis and a best management of the disease. Methods: A questionnaire was sent to the Italian liver centres to collect data on demographic features, history of prematurity