RESUMO
The genetically determined acetylator phenotype in diabetic children with and without increased urinary albumin excretion was investigated. Acetylator phenotype was determined according to Evans, and 24-hour albumin excretion rate (AER) was measured by immunoturbidometry in 86 children and adolescents with type 1 (insulin-dependent) diabetes mellitus and in 100 age-matched healthy controls. In diabetics, the fast acetylator phenotype was found in 36 (41.9%) patients and the slow one in 50 (58.1%); the control group had 52 (52%) fast and 48 (48%) slow acetylators. There were no significant differences in acetylator phenotypes between diabetic patients and control subjects (chi 2 = 1.0, NS). Among patients with normal albumin excretion (n = 70, mean age: 12.9 +/- 3.5 years, mean diabetes duration: 5.3 +/- 3.8 years, AER < 20 micrograms/min), 35 (50%) fast acetylators and 35 (50%) slow acetylators were found. In patients with elevated albumin excretion (n = 16, mean age: 14.0 +/- 3.2 years, mean diabetes duration: 4.9 +/- 3.0 years, AER > 20 micrograms/min), 1 (6.3%) patient was a fast acetylator and 15 (93.7%) were slow acetylators. A significant difference has been found between the two groups in the rate of fast/slow acetylators (chi 2 = 8.79, p < 0.01). The strong correlation between the slow acetylator phenotype and microalbuminuria in diabetics suggests that: (a) genetic factors may play a role in the development of diabetic nephropathy; (b) the acetylator status could be a useful tool to detect patients 'at risk' of nephropathy.
Assuntos
Albuminúria , Diabetes Mellitus Tipo 1/genética , Fenótipo , Acetilação , Adolescente , Criança , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/genética , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Similar doses of a drug given to different individuals can result in widely disparate plasma concentrations and hence effects. Beside intraindividual differences also inter-ethnic differences of drug response must be taken into consideration. Both inter-individual and inter-ethnic variations of drug response are mostly related to genetic factors (polymorphism) involved in drug metabolism and kinetics. The farmacogenetic disorders involved clinically result in pharmacogenetic side effects. In order to avoid pharmacogenetic side effects, beside phenotyping of the patients, selection of drugs subjected to different pharmacogenetic disorders may be of great clinical importance. Therefore, a scoring method was carried out for the selection of pharmacogenetically hazardous drugs. With regard to both genetic and environmental factors influencing the drug response, 140 suspicious drugs were studied and classified with the method. Eighteen was the maximum point value for genetic and 12 for contributing factors involved, so 30 was the maximum point number in each drug studied. Out of 140 substances 50 drugs (qualified with 20 points or more) proved to be hazardous in different pharmacogenetic disorders, among them several widely used agents, e.g. Diazepam, Isoniazid, Phenytoin, Warfarin, Quinidine, Tolbutamide, etc. The article sums up the findings in a Table and comments them. This scoring method may be useful in drug safety and preventive medicine.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Polimorfismo Genético , Acetilação , Feminino , Humanos , Hidroxilação , Masculino , Oxirredução , Preparações Farmacêuticas/metabolismo , Farmacogenética , Fenótipo , Fatores de RiscoAssuntos
Debrisoquina/metabolismo , Isoquinolinas/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hungria , Hidroxilação , Masculino , FenótipoRESUMO
The distribution of drug acetylator phenotypes in 100 healthy newborn infants was studied and compared with the acetylator phenotypes frequency in different age groups. Phenotyping was performed by assaying total and free sulphadimidine in the urine after single oral test dose of the drug/100 mg. As in elderly subjects, slow acetylator phenotype was predominant also in healthy newborns (83%), which was the highest frequency of all age groups observed. Acetylator phenotype in the newborn infants may be influenced by genetic, environmental (e.g., nutritive), as well as by developmental factors (e.g., postnatal enzyme deficiency, age-specific changes in organ functions, etc.). In this connection, slow acetylator phenotype of the neonate may be related to a negative pantothenic acid balance causing insufficient Coenzyme-A synthesis, too. The predominance of the slow acetylator phenotype resulting in higher drug sensitivity can be regarded clinically as a special risk factor in human neonates.
