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• W1602363809 abstract "To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of betaine in the treatment of classical homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency with a view to optimizing the dosage regimen.Betaine was given as a single oral dose of 100 mg kg(-1) to six patients (age range 6-17 years) who normally received betaine but whose treatment had been suspended for 1 week prior to the study. Plasma betaine and total homocysteine concentrations were measured by high performance liquid chromatography (h.p.l.c.) at frequent intervals over 24 h. The best-fit PK model was determined using the PK-PD program Win-Nonlin and the concentration-time-effect data analysed by an indirect PD model. Using the PK and PD parameters, simulations were carried out with the aim of optimizing betaine dosage.Betaine PK was described by both mono- and bi-exponential disposition functions with first order absorption and a lag time. The correlation coefficient between betaine oral clearance and body weight was 0.6. Mean betaine clearance was higher in males than in females (P=0.03). PK-PD simulation indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg kg(-1) day(-1) dosage for betaine.PK-PD modelling allows recommendations for optimal dosage of betaine in the treatment of homocystinuria, that have the potential for improved patient compliance and both therapeutic and pharmacoeconomic benefit." @default.
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• W1602363809 date "2002-08-01" @default.
• W1602363809 modified "2023-09-27" @default.
• W1602363809 title "An indirect response model of homocysteine suppression by betaine: optimising the dosage regimen of betaine in homocystinuria" @default.
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• W1602363809 doi "https://doi.org/10.1046/j.1365-2125.2002.01620.x" @default.
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