RESUMO
OBJECTIVE: To determine whether cytochrome P450 (CYP)2C19 haplotype associates with lansoprazole-associated adverse event frequency. STUDY DESIGN: Respiratory adverse events from a clinical trial of lansoprazole in children with asthma were analyzed for associations with extensive or poor metabolizer (PM) phenotype based on CYP2C19 haplotypes. Carriers of CYP2C19*2, *3, *8, or *9 alleles were PMs; carriers of 2 wild-type alleles were extensive metabolizers (EMs). Plasma concentrations of lansoprazole were determined in PM and EM phenotypes. RESULTS: The frequency of upper respiratory infection among PMs (n = 45) was higher than that among EMs (n = 91), which in turn was higher than that in placebo subjects (n = 135; P = .0039). The frequency of sore throat (ST) was similarly distributed among EMs and PMs (P = .0015). The OR (95% CI) for upper respiratory infections in PMs was 2.46 (1.02-5.96) (P = .046); for EMs, the OR (95% CI) was 1.55 (0.86-2.79). The OR (95% CI) for ST in EMs and PMs was 2.94 (1.23-7.05, P = .016) vs 1.97 (1.09-3.55, P = .024), respectively. Mean ± SD plasma concentrations of lansoprazole were higher in PMs than in EMs: 207 ± 179 ng/mL vs 132 ± 141 ng/mL (P = .04). CONCLUSIONS: Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings.
Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/efeitos adversos , Hidrocarboneto de Aril Hidroxilases/genética , Asma/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Inibidores da Bomba de Prótons/efeitos adversos , Infecções Respiratórias/induzido quimicamente , 2-Piridinilmetilsulfinilbenzimidazóis/farmacocinética , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Adolescente , Asma/genética , Bronquite/induzido quimicamente , Bronquite/genética , Criança , Citocromo P-450 CYP2C19 , Feminino , Marcadores Genéticos , Técnicas de Genotipagem , Haplótipos , Humanos , Lansoprazol , Modelos Logísticos , Masculino , Razão de Chances , Faringite/induzido quimicamente , Faringite/genética , Inibidores da Bomba de Prótons/farmacocinética , Inibidores da Bomba de Prótons/uso terapêutico , Infecções Respiratórias/genéticaRESUMO
OBJECTIVES: We studied a novel pancreatic enzyme product, ALTU-135, a proprietary formulation of microbially derived lipase, protease, and amylase, to determine its efficacy and safety in treatment of pancreatic insufficiency (PI) in patients with cystic fibrosis (CF). STUDY DESIGN: Ambulatory subjects with CF-PI (n = 117) had baseline coefficient of fat and nitrogen absorption (CFA and CNA, respectively) determined in an inpatient setting while not receiving pancreatic enzyme replacement therapy. Subjects were then randomized to treatment with ALTU-135 containing 5000 (low), 25,000 (mid), or 100,000 (highest) units of lipase (1:1:0.15 of lipase:protease:amylase) for 28 days. After 14 days, CFA and CNA were re-measured. The primary outcomes were change from baseline in CFA and CNA between treatments. RESULTS: Treatment CFA was significantly greater in the mid and highest dose groups compared with that in the low dose group (P = .0229 and P =.0041, respectively); findings were similar for CNA. Subjects with baseline CFA < or = 40% and > 40% in the 2 higher dose groups had a mean increase of 31 and 8 percentage points in CFA, respectively (P < .0001). CONCLUSION: ALTU-135 was efficacious during the 1-month study period at the dose of 25,000 units of lipase, 25,000 units of protease, and 3750 units of amylase.
Assuntos
Amilases/uso terapêutico , Fibrose Cística/complicações , Insuficiência Pancreática Exócrina/tratamento farmacológico , Insuficiência Pancreática Exócrina/enzimologia , Lipase/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Adolescente , Adulto , Amilases/administração & dosagem , Amilases/efeitos adversos , Análise de Variância , Glicemia/metabolismo , Criança , Fibrose Cística/enzimologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Insuficiência Pancreática Exócrina/complicações , Gorduras/análise , Gorduras/metabolismo , Fezes/química , Feminino , Seguimentos , Humanos , Absorção Intestinal/efeitos dos fármacos , Lipase/administração & dosagem , Lipase/efeitos adversos , Masculino , Nitrogênio/análise , Nitrogênio/metabolismo , Peptídeo Hidrolases/administração & dosagem , Peptídeo Hidrolases/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the safety of budesonide inhalation suspension (BIS) with placebo in infants 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze. STUDY DESIGN: In this multicenter, randomized, double-blinded, parallel-group, placebo-controlled study, 141 patients received 0.5 mg BIS (n = 48), 1.0 mg BIS (n = 44), or placebo (n = 49) once daily for 12 weeks. The primary variable was adrenal function, based on cosyntropin-stimulated plasma cortisol levels. Spontaneous adverse events and clinical laboratory findings also were monitored. RESULTS: Overall, the types and frequencies of adverse events reported during the study were comparable across treatment groups. The response to cosyntropin stimulation was similar across treatment groups, with no significant difference between BIS treatment and placebo. CONCLUSIONS: The safety profile of BIS was similar to that of placebo, with no suppressive effect on adrenal function in patients 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze.