Abstract | AIMS: METHODS:
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. RESULTS:
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. CONCLUSIONS: 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.
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Authors | Angela Matthews, Trevor N Johnson, Amin Rostami-Hodjegan, Anupam Chakrapani, J Edward Wraith, Stuart J Moat, James R Bonham, Geoffrey T Tucker |
Journal | British journal of clinical pharmacology
(Br J Clin Pharmacol)
Vol. 54
Issue 2
Pg. 140-6
(Aug 2002)
ISSN: 0306-5251 [Print] England |
PMID | 12207633
(Publication Type: Journal Article)
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Chemical References |
- Homocysteine
- Betaine
- Cystathionine beta-Synthase
- Pyridoxine
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Topics |
- Administration, Oral
- Adolescent
- Betaine
(administration & dosage, pharmacokinetics, pharmacology)
- Child
- Cystathionine beta-Synthase
(deficiency)
- Dose-Response Relationship, Drug
- Female
- Homocysteine
(antagonists & inhibitors, blood)
- Homocystinuria
(drug therapy, etiology, metabolism)
- Humans
- Male
- Pyridoxine
(therapeutic use)
- Treatment Failure
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