Abstract
Objective: To investigate time dependent changes in the formation of 7-hydroxymethotrexate (7OH-MTX) from methotrexate (MTX) in patients undergoing treatment for psoriasis with MTX. Method: This study is a companion piece of the study by Chladek et al. therefore the data from the study cited here was used. For modeling purposes a modeling method based on the theory of dynamic systems was employed. Results: The metabolic ratios of MTX to 7OH-MTX in plasma were constant during the first three months of the treatment of the patients for psoriasis with MTX. However, the mean time of the formation of 7OH-MTX from MTX increased from the value of about 9.35 h in the first phase of treatment to the value of about 15.59 in the third phase of treatment. The rate of the formation of 7OH-MTX from MTX decreased from 0.51/h to 0.29 1/h during the same time interval. Conclusions: All models developed; successfully described the data of all patients enrolled in the previous study by Chladek et al. the modeling method used is universal. Therefore, it can be used to develop mathematical models not only in pharmacokinetics but also in several other scientific and practical fields.
Highlights
In current study, 7-hydroxymethotrexate (7OH-MTX) from methotrexate (MTX) was performed in the same time interval
The investigation started with the definition of patient-specific dynamic systems, denoted by H, in the Laplace domain [4,5,6,7,8,9,10]
Dynamic systems H were defined in such a way that the Laplace transforms of the plasma concentration-time profiles of MTX (Figure 1) were used as the inputs to dynamic systems H and the Laplace transforms of the plasma concentration-time profiles of 7OH-MTX (Figure 2) were used as the outputs of the dynamic systems H
Summary
The metabolic ratios of MTX to 7OH-MTX in plasma were constant during the first three months of the treatment of the patients for psoriasis with MTX. The rate of the formation of 7OH-MTX from MTX decreased from 0.51/h to 0.29 1/h during the same time interval
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