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KMID : 1146920220520030331
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Journal of Pharmaceutical Investigation
2022 Volume.52 No. 3 p.331 ~ p.339
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Population pharmacokinetic modeling and simulation of choline in healthy Korean subjects after oral administration of choline alfoscerate
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Im Ae-Gyeoing
Choi Go-Wun
Kang Dong-Wook
Cho Seok-Jin
Kim Jae-Hee
Kim Kyu-Yeon
Cho Hea-Young
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Abstract
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Purpose: This study aimed to investigate clinical pharmacokinetics (PKs) of choline after oral administration of choline alfoscerate capsule and newly developed syrup formulation using population pharmacokinetic modeling and simulation approach.
Methods: Each subject received 1,200 mg single administration of choline alfoscerate capsule or syrup. Blood collection was performed 13 times each day before administration and on the day of administration. Baseline blood was collected to investigate the circadian rhythm of endogenous substance of choline. A PK model of choline was developed to describe baseline circadian wave and its absorption and disposition characteristics after oral administration of exogenous choline substances. Furthermore, the developed model was used to generate stochastic simulation data for investigating choline exposure with a regimen of clinical practice settings.
Results: The one-compartment with circadian input, first-order absorption, and first-order elimination well described the plasma concentration of choline. Baseline circadian wave was described using cosine function with parameters of baseline concentration (C0), amplitude (Amp), and time shift to peak (Tshift). Intrinsic choline concentration followed a typical circadian rhythm. Exogenous choline substance increased the endogenous choline concentration. Furthermore, three times daily dosing of choline alfoscerate increased choline exposure than once a day administration with the same amount of choline alfoscerate.
Conclusion: This is the first study investigating PKs of choline alfoscerate using pharmacokinetic modeling, including circadian input function to ameliorate physiological and pharmacological properties of choline. Results of this study provide meaningful information for evaluating clinical effectiveness of choline alfoscerate.
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KEYWORD
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Choline alfoscerate, Endogenous substance, Circadian rhythm, Population pharmacokinetics
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