The polymorphic 4-hydroxylation of debrisoquine in a Saudi arab population. 1980

S I Islam, and J R Idle, and R L Smith

1. Debrisoquine 4-hydroxylation was polymorphic in 102 Saudi arab volunteers, the population comprising one phenotypically poor metabolizer and 101 phenotypically extensive metabolizers of debrisoquine. 2. Mean urinary recoveries of drug and metabolite were low in Saudis (15 +/- 10% dose, mean +/- S.D.), which compared well with previously studied populations of Egyptians (16%) and Ghanaians (18%), but which were lower than those seen in a UK white population (41%). 3. Saudis, like Egyptians, were more extensive metabolizers of debrisoquine than UK whites, as judged by the metabolic ratio (% dose as debrisoquine/% dose as 4-hydroxy-debrisoquine eliminated in the urine). 4. Neither sex, urine collection period nor urinary recovery of drug and metabolite had any statistically significant effect upon the distribution of metabolic ratios in Saudis. 5. The frequency of the DL allele controlling the recessive poor metabolizer trait was 0.099 +/- 0.049 (+/- S.E.M.) in Saudis, which compared well to Egyptians (0.118 +/- 0.059) but was significantly lower than that for UK whites (0.298 +/- 0.030). 6. These findings raise questions regarding the efficacy and safety in Saudis of drugs undergoing oxidative metabolism which have been evaluated for usage in European white subjects.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D003647 Debrisoquin An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism. Debrisoquine,Tendor
D005260 Female Females
D005828 Genetics, Population The discipline studying genetic composition of populations and effects of factors such as GENETIC SELECTION, population size, MUTATION, migration, and GENETIC DRIFT on the frequencies of various GENOTYPES and PHENOTYPES using a variety of GENETIC TECHNIQUES. Population Genetics
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006900 Hydroxylation Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed) Hydroxylations
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths

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