Six-month, prospective, longitudinal, open-label caffeine and dextromethorphan phenotyping study in children with growth hormone deficiency receiving recombinant human growth hormone replacement
| Autor: | Ned B. Smith, Gregory L. Kearns, Mary Jayne Kennedy, Andrea Gaedigk, Daniel A. Davis, Robin E. Pearce |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Xanthine Oxidase Adolescent Arylamine N-Acetyltransferase Urine Short stature Dextromethorphan Growth hormone deficiency Cytochrome P-450 CYP1A2 Dextrorphan Internal medicine Caffeine medicine Humans Pharmacology (medical) Longitudinal Studies Prospective Studies Insulin-Like Growth Factor I Child Dwarfism Pituitary Growth Disorders Pharmacology business.industry Human Growth Hormone medicine.disease Recombinant Proteins Somatropin Endocrinology Phenotype Cytochrome P-450 CYP2D6 Child Preschool Population study Central Nervous System Stimulants Female medicine.symptom business Pediatric pharmacology medicine.drug |
| Zdroj: | Clinical therapeutics. 30(9) |
| ISSN: | 0149-2918 |
| Popis: | Recombinant human growth hormone (r-hGH) is increasingly being used in children. Although growth hormone (GH) may alter the clearance of concomitantly administered medications, its effects on individual drug-metabolizing enzymes in children have not been characterized.The goal of this study was to assess the activities of cytochrome P450 (CYP) 1A2, N-acetyltransferase 2, xanthine oxidase, and CYP2D6 in children with isolated idiopathic GH deficiency before and 3 and 6 months after initiation of r-hGH treatment.This 6-month, prospective, longitudinal, open-label phenotyping study was conducted at 4 academic tertiary care centers within the Pediatric Pharmacology Research Unit network. Prepubertal or early pubertal children (4-14 years) with short stature and isolated idiopathic GH deficiency were enrolled. Patients were given 4 ounces of a cola beverage and 0.5 mg/kg of dextromethorphan (DM) before and 3 and 6 months after initiation of r-hGH treatment. Urine was collected for 8 hours after probe substrate administration, and enzyme activity was assessed using validatedcaffeine/metaboliteandDM/metabolitemolar ratios. Patients with a DM/dextrorphan molar ratioor =0.3 were classified as poor metabolizers, and those with a ratio0.3 were classified as extensive metabolizers. Anthropometric and biochemical responses were assessed at each visit. Blood was also obtained for determination of serum insulinlike growth factor-1 (IGF-1) levels and CYP2D6 genotype.Fourteen patients (mean [SD] age, 11.5 [2.6] years [age range, 4.5-14.6 years]; 11 males, 3 females; 100% white; median height and weight, 131.8 cm and 29.2 kg, respectively) completed the 3 study visits. However, data from 2 patients were excluded from analysis due to procedural violations. In all patients, growth velocity and serum IGF-1 concentrations were significantly higher (P0.001) after r-hGH treatment (mean doses, 0.32 and 0.33 mg/kg per week at 3 and 6 months, respectively). However, molar ratio values did not significantly change after initiation of r-hGH.In this study population of children with isolated idiopathic GH deficiency, no significant differences in caffeine/metabolite and DM/metabolite molar ratios were observed after initiation of r-hGH treatment. |
| Databáze: | OpenAIRE |
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