Electronic Resource
Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency
| العنوان: | Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency |
|---|---|
| المؤلفون: | Zurflüh, M., Fiori, L., Fiege, B., Ozen, I., Demirkol, M., Gärtner, K., Thöny, B., Giovannini, M., Blau, N. |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Summary: The oral loading test with tetrahydrobiopterin (BH4) is used to discriminate between variants of hyperphenylalaninaemia and to detect BH4-responsive patients. The outcome of the loading test depends on the genotype, dosage of BH4, and BH4 pharmacokinetics. A total of 71 patients with hyperphenylalaninaemia (mild to classic) were challenged with BH4 (20 mg/kg) according to different protocols (1 × 20 mg or 2 × 20 mg) and blood BH4 concentrations were measured in dried blood spots at different time points (T0, T2, T4, T8, T12, T24, T32 and T48 h). Maximal BH4 concentrations (median 22.69 nmol/g Hb) were measured 4 h after BH4 administration in 63 out of 71 patients. Eight patients presented with maximal BH4 concentrations ∼44% higher at 8 h than at 4 h. After 24 h, BH4 blood concentrations dropped to 11% of maximal values. This profile was similar using different protocols. The following pharmacokinetic parameters were calculated for BH4 in blood: t max = 4 h, AUC (T0−32) = 370 nmol × h/g Hb, and t 1/2 for absorption (1.1 h), distribution (2.5 h), and elimination (46.0 h) phases. Maximal BH4 blood concentrations were not significantly lower in non-responders and there was no correlation between blood concentrations and responsiveness. Of mild PKU patients, 97% responded to BH4 administration, while one was found to be a non-responder. Only 10/19 patients (53%) with Phe concentrations of 600-1200 μmol/L responded to BH4 administration, and of the patients with the severe classical phenotype (blood Phe > 1200 μmol/L) only 4 out of 17 patient responded. An additional 36 patients with mild hyperphenylalaninaemia (HPA) who underwent the combined loading test with Phe+BH4 were all responders. Slow responders and non-responders were found in all groups of HPA |
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| الاتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| Other Numbers: | CHRRO oai:doc.rero.ch:317991 1043542429 |
| المصدر المساهم: | RERO-LIBR NETWORK OF WESTERN SWITZERLAND From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1043542429 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |