Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR-1, CYP3A4, and CYP3A5 genes

T SNPs. For a typical 70-kg white patient, the following parameters were estimated: absorption rate constant, 1.27 h -1; absorption time lag, 0.47 hour; oral volume of distribution of the central and peripheral compartment, 56.3 and 185.0 L, respectively; oral clearance (Cl/F), 30.7 L/h; and oral intercompartmental clearance, 31.7 L/h. Estimated interpatient variability of Cl/F was 28%. Cl/F was significantly correlated with weight and ethnicity; Cl/F was 13% higher (95% confidence interval, 8%-18%; P -->
Jazyk: English
ISSN: 0009-9236
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=narcis______::b72c44b4809a38ad9839c84a2c916839
https://pure.amc.nl/en/publications/population-pharmacokinetics-of-cyclosporine-in-kidney-and-heart-transplant-recipients-and-the-influence-of-ethnicity-and-genetic-polymorphisms-in-the-mdr1-cyp3a4-and-cyp3a5-genes(97ab9759-03ee-4402-96d7-0276c960ff17).html
Rights: RESTRICTED
Přírůstkové číslo: edsair.narcis........b72c44b4809a38ad9839c84a2c916839
Autor: Hesselink, Dennis A., van Gelder, Teun, van Schaik, Ron H. N., Balk, Aggie H. M. M., van der Heiden, Ilse P., van Dam, Thea, van der Werf, Marloes, Weimar, Willem, Mathot, Ron A. A.
Přispěvatelé: Other departments
Jazyk: angličtina
Rok vydání: 2004
Zdroj: Clinical pharmacology and therapeutics, 76(6), 545-556. Wiley-Blackwell
ISSN: 0009-9236
Popis: Our objective was to determine the relationship between single nucleotide polymorphisms (SNPs) in the multidrug resistance 1 (MDR-1) gene and the cytochrome P450 (CYP) genes CYP3A4 and CYP3A5 and the pharmacokinetics of cyclosporine (INN, ciclosporin). Cyclosporine pharmacokinetics of 151 kidney and heart transplant recipients undergoing maintenance therapy was described by use of nonlinear mixed-effects modeling (NONMEM) according to a 2-compartment pharmacokinetic model with first-order absorption and elimination. All patients were genotyped for the CYP3A4*1B and *3 , CYP3A5*3 and *6 , and MDR-1 3435C-->T SNPs. For a typical 70-kg white patient, the following parameters were estimated: absorption rate constant, 1.27 h -1; absorption time lag, 0.47 hour; oral volume of distribution of the central and peripheral compartment, 56.3 and 185.0 L, respectively; oral clearance (Cl/F), 30.7 L/h; and oral intercompartmental clearance, 31.7 L/h. Estimated interpatient variability of Cl/F was 28%. Cl/F was significantly correlated with weight and ethnicity; Cl/F was 13% higher (95% confidence interval, 8%-18%; P
Databáze: OpenAIRE
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