RESUMO
The efficacy of proton pump inhibitor (PPI) medications is highly dependent on plasma concentrations, which varies considerably due to cytochrome P450 (CYP2C19) genetic variation. We conducted a pragmatic, pilot study of CYP2C19 genotype-guided pediatric dosing of PPI medications. Children aged 5-17 years old with gastric-acid-related conditions were randomized to receive either conventional dosing of a PPI or genotype-guided dosing for a total of 12 weeks. Sixty children (30 in each arm) were enrolled and had comparable baseline characteristics. The mean daily omeprazole equivalent dose prescribed to participants across metabolizer phenotype groups was significantly different in the genotype-guided dosing arm (P < 0.001), but not in the conventional dosing arm. Prescribers waited for the genotype result before prescribing the PPI medication for 90% of the participants in the genotype-guided dosing arm. The number of participants who reported an infection was marginally lower in genotype-guided dosing vs. conventional dosing (20% vs. 44%; P = 0.07). Sinonasal symptoms were higher in the conventional dosing arm as compared with genotype-guided dosing arm: (2.6 (2.0, 3.4) vs. 1.8 (1.0, 2.3), P = 0.031). CYP2C19 genotype-guided PPI therapy is feasible in a clinical pediatric setting, well accepted by providers, resulted in differential PPI dosing, and may reduce PPI-associated infections. A future large scale randomized clinical trial of CYP2C19 genotype-guided pediatric dosing of PPI medications in children is warranted.
Assuntos
Citocromo P-450 CYP2C19/genética , Refluxo Gastroesofágico/tratamento farmacológico , Medicina de Precisão/métodos , Inibidores da Bomba de Prótons/administração & dosagem , Adolescente , Criança , Pré-Escolar , Citocromo P-450 CYP2C19/metabolismo , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Estudos de Viabilidade , Feminino , Seguimentos , Refluxo Gastroesofágico/genética , Técnicas de Genotipagem , Humanos , Masculino , Projetos Piloto , Inibidores da Bomba de Prótons/farmacocinéticaRESUMO
BACKGROUND: Single-stage PEG buttons (PEG-B) allow initial placement of a skin-level gastrostomy device for children who require enteral access. They offer significant advantages over traditionally placed PEG tubes (PEG-T) but have not been widely accepted into practice. OBJECTIVE: To review our experience with PEG-Bs compared with PEG-Ts. HYPOTHESIS: PEG-B shares a similar safety profile with PEG-T but delays the need for an initial device change well beyond the change that usually occurs at 6 to 8 weeks after PEG-T placement. DESIGN: Retrospective chart review. SETTING: Nemours Children's Clinic, Jacksonville, Florida. PATIENTS: All children undergoing both PEG procedures and attending our clinic from 1997 to 2002. MAIN OUTCOME MEASUREMENTS: Age, sex, weight, indications, postoperative complications, interval until first tube change and first tube change complications. RESULTS: Totals of 145 and 93 patients were identified in the PEG-B and PEG-T groups, respectively. Patient characteristics were similar in the 2 groups with respect to age, weight, indications, and postoperative complications. The interval until first tube change, however, was significantly longer in the PEG-B group (314 days) than in the PEG-T (78 days) (P < .0001). In addition, the PEG-B was found to be as safe as the PEG-T for small infants who weighed less than 5 kg. CONCLUSIONS: PEG-B placement should be considered as the procedure of choice over PEG-T placement for children. It offers similar safety profiles, even for small patients and a significantly longer interval until first device change.
