Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants

Y. K. Lyauk; C. Stage; T. K. Bergmann; L. Ferrero-Milliani; D. Bjerre; R. Thomsen; K. P. Dalhoff; H. B. Rasmussen; G. Jürgens

doi:10.1111/cts.12423

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants

Y. K. Lyauk^*
, C. Stage
, T. K. Bergmann
, L. Ferrero-Milliani
, D. Bjerre
, R. Thomsen
, K. P. Dalhoff
, H. B. Rasmussen
, G. Jürgens

^*Corresponding author for this work

Clinical Pharmacological Unit

Research output: Contribution to journal › Article › Research › peer-review

Abstract

The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d-MPH plasma exposure.

Original language	English
Pages (from-to)	337-345
Number of pages	9
Journal	Clinical and Translational Science
Volume	9
Issue number	6
DOIs	https://doi.org/10.1111/cts.12423
Publication status	Published - 1 Dec 2016

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10.1111/cts.12423

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Lyauk, Y. K., Stage, C., Bergmann, T. K., Ferrero-Milliani, L., Bjerre, D., Thomsen, R., Dalhoff, K. P., Rasmussen, H. B., & Jürgens, G. (2016). Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants. Clinical and Translational Science, 9(6), 337-345. https://doi.org/10.1111/cts.12423

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title = "Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants",

abstract = "The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d-MPH plasma exposure.",

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Lyauk, YK, Stage, C, Bergmann, TK, Ferrero-Milliani, L, Bjerre, D, Thomsen, R, Dalhoff, KP, Rasmussen, HB & Jürgens, G 2016, 'Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants', Clinical and Translational Science, vol. 9, no. 6, pp. 337-345. https://doi.org/10.1111/cts.12423

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AU - Lyauk, Y. K.

AU - Stage, C.

AU - Bergmann, T. K.

AU - Ferrero-Milliani, L.

AU - Bjerre, D.

AU - Thomsen, R.

AU - Dalhoff, K. P.

AU - Rasmussen, H. B.

AU - Jürgens, G.

PY - 2016/12/1

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AB - The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d-MPH plasma exposure.

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JO - Clinical and Translational Science

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ER -

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants

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