N‐acetylation phenotyping with dapsone in a mainland Chinese population.

Horai, Yukio; Zhou, HH; Zhang, LM; Ishizaki, Takashi

doi:10.1111/j.1365-2125.1988.tb03285.x

Cited by 24 publications

(15 citation statements)

References 21 publications

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“…Individuals with the ratio between these two values were classified as indeterminate acetylators. This standard phenotyping method using plasma samples was compared with the use of urinary MADDS/DDS ratio measured in sample collected during the postdose 0-6 h period as performed in our recent study (Horai et al, 1988).…”

Section: Methodsmentioning

confidence: 99%

“…There are considerable interethnic differences in the proportion of acetylator phenotypes (Lunde et al, 1977;Clark, 1985): populations of Caucasians show an approximately equal percentage of slow and rapid acetylators. In contrast, the incidence of slow acetylators is markedly low in Orientals, such that it shows only about 10% in Japanese (Sunahara et al, 1961;Horai et al, 1982), 13% in a mainland Chinese (Horai et al, 1988), and 22% in Chinese populations residing outside the mainland of China (Evans, 1986;Horai et al, 1988). Polymorphic N-acetylation has been linked to variation in drug response, susceptibility to adverse reaction, and to increased incidence of certain spontaneous disorders including SLE and even cancer (Weber et al, 1983;Evans, 1984;Clark, 1985;Weber & Hein, 1985;Evans, 1986).…”

Section: Introductionmentioning

confidence: 92%

“…Since phenotyping with DDS has been shown to give results comparable with those using the elimination half-life of isoniazid or the urinary excretion ratio of acetylsulphamethazine to sulphamethazine (Gelber et al, 1971;Hanson et al, 1981), and its simplicity for phenotyping (Reidenberg et al, 1975), DDS has been used as a model drug for determining the acetylator phenotype (Gelber et al, 1971;Reidenberg et al, 1975;Carr et al, 1978;Cartwright et al, 1982;Philip et al, 1984Philip et al, , 1988Horai et al, 1988). Using an oral DDS (100 mg) as the test probe and the plasma MADDS to DDS ratio at 3 h postdose, we have recently reported that the incidence of slow acetylators (MADDS/DDS < 0.30) is 13.0% in an unrelated mainland Chinese population (14 of the 108 subjects) and that the urinary acetylation ratio after the oral dose of DDS is not a discriminative index for determining acetylation phenotype (Horai et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…Using an oral DDS (100 mg) as the test probe and the plasma MADDS to DDS ratio at 3 h postdose, we have recently reported that the incidence of slow acetylators (MADDS/DDS < 0.30) is 13.0% in an unrelated mainland Chinese population (14 of the 108 subjects) and that the urinary acetylation ratio after the oral dose of DDS is not a discriminative index for determining acetylation phenotype (Horai et al, 1988). However, no data are available regarding the Nacetylation polymorphism of DDS or the relationship between plasma and urine acetylation ratios in Japanese.…”

Section: Introductionmentioning

confidence: 99%

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N‐acetylation polymorphism of dapsone in a Japanese population.

Horai

Ishizaki

1988

Brit J Clinical Pharma

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1 The N-acetylation of dapsone (DDS) was studied in 182 unrelated healthy Japanese subjects. The frequency of slow acetylators determined using the plasma monoacetyldapsone (MADDS) to DDS ratio (MADDS/DDS, slow acetylators < 0.30 and rapid acetylators > 0.35) at 3 h after an oral dose of DDS (100 mg) was 6.6% (12 of the 182 subjects) with a 95% confidence interval of 3.8 to 11.2%. 2 The frequency distribution histogram of the plasma MADDS/DDS ratio showed an apparent trimodal pattern. However, the numbers of heterozygous (n = 105) and homozygous rapid acetylators (n = 65) derived from the observed data did not agree with those predicted for the respective rapid acetylators (n = 70, and n = 100) by applying the Hardy-Weinberg Law, when the suggested antimode of 0.85 discriminating these two rapid acetylators was employed. 3 The incidence of slow acetylators was unexpectedly lower in the males (1.4%, 1 of the 69 subjects, with a 95% confidence interval of 0.2 to 7.7%) compared with the incidence in the females (9.7%, 11 of the 113 subjects, with a 95% confidence interval of 5.5 to 16.6%). The difference reached a marginally significant level (Fisher's exact probability test, P = 0.02). 4 The mean plasma concentration of MADDS was significantly (P < 0.001) lower in the slow compared to the rapid acetylators and there was a highly significant correlation (rs = 0.757, P < 0.001) between plasma MADDS levels and MADDS/DDS ratios. 5 Slow acetylators showed a significantly (P < 0.001) lower urinary MADDS/DDS ratio and excreted less (P < 0.001) MADDS than rapid acetylators. Although there was a highly significant relationship (r, = 0.612, P < 0.001) between plasma and urinary acetylation ratios, the latter was not in complete concordance with the phenotyping derived from the plasma acetylation ratios. Therefore, measurement of a urinary acetylation ratio (MADDS/ DDS) was confirmed not to be a non-invasive phenotyping method.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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N‐acetylation polymorphism of dapsone in a Japanese population.

Horai

Ishizaki

1988

Brit J Clinical Pharma

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“…This mortality rate is further supported by another study conducted in Victoria published in 2005, which described a hospital mortality of 28.9% for septic patients needing intensive care (21,25). …”

Section: Sepsismentioning

confidence: 54%

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Tsai¹

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Sepsis is a major health issue in the Australian Indigenous population. Unfortunately, the high rates of mortality and morbidity caused by sepsis or severe sepsis in this population have not significantly reduced over recent decades. Research into the role of optimisation of antibiotic therapy for improving patient outcomes is certainly an important area of need. In other patient populations, there is increasing evidence of an improvement of clinical cure rates and survival in patients with severe sepsis when antibiotic dosing results in therapeutic concentrations, that is, achieves pharmacokinetic/pharmacodynamic (PK/PD) targets. However, numerous PK changes caused by the altered physiology associated with critical illness may reduce the likelihood of such effective dosing.Previous studies have identified a number of physiological characteristics in the Australian Indigenous population which suggest that interethnic PK differences are likely in comparison with the non-Indigenous. As most PK data of antibiotics were obtained from healthy Caucasian volunteers, whether these data can be extrapolated to the critically ill Indigenous patients requires investigation.The aims of this thesis are to describe the PK of meropenem, ceftriaxone, vancomycin and piperacillin in severely septic Indigenous patients; compare the PK with existing data from nonIndigenous patients; design optimised dosing regimens for each of the study antibiotics; and quantify the variation in renal function of critically ill Indigenous patients. This thesis consists of nine Chapters:Chapter one provides an overview of the current clinical challenges encountered in antibiotic dosing in critically ill patients. It also discusses specific physiological characteristics of Australian Indigenous patients which may lead to different PK compared with non-Indigenous comparators.Chapter two comprises of a narrative review which discusses the PK/PD factors that should be considered when prescribing antibiotics to critically ill patients. This Chapter summarises data which describe an improvement in clinical outcome when antibiotics achieve PK/PD targets. ThisChapter concludes to support an individualised approach to dosing antibiotics as opposed to the 'one dose fits all' approach that is common to clinical practice.ii Chapter three incorporates a systematic review which investigates the published data describing differences in antibiotic PK between different ethnic groups. No reports on PK in Indigenous Australians were found. The predominant data described differences in PK between the Asian and Caucasian ethnicities. Typically, Asian subjects manifested higher antibiotic concentrations for antibiotics that have significant hepatic metabolism, are substrates to p-glycoprotein or other forms of active transport and/or have high alpha-1-acid glycoprotein binding.Chapter four incorporates a study which described the renal function of critically ill Australian Indigenous patients. This study found a numerically higher incidence of augmented renal clea...

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Acetylation phenotype status in a Bangladeshi population and its comparison with that of other Asian population data

Zaid

Nargis

Neelotpol

et al. 2004

Biopharm & Drug Disp

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The objective of the present study was to determine the acetylator status of the Bangladeshi population and to compare the findings with the acetylator status of other Asian populations. The acetylator phenotype was determined in 517 unrelated healthy Bangladeshi subjects. The phenotyping procedure was done according to Price Evans' method using the NAT2 specific probe drug--sulphadimidine. The Bangladeshi population showed a bimodal distribution of fast and slow acetylators. Of a total of 517 healthy Bangladeshi, 79.5% (n=411) were fast acetylators and the rest 20.5% (n=106) were slow acetylators. The high frequency of the fast acetylators in the population of Bangladesh was comparable to other populations in East Asia. When this acetylator status was compared with other Asian data, the Asian population showed a positive correlation between the acetylator status and the geographical longitude (r=0.919; t=7.37; p>0.001; d.f.=10). The regression line of the scatter diagram showed that the frequency of acetylating capacity increasingly occurred in the populations towards eastern Asia (regression coefficient=0.54; constant=52.36). This line was termed as the Asian fast acetylator longitude (AFAL). Thus the AFAL was able to predict the acetylator status of the Asian population by the east-west geographical longitude. The AFAL could be a useful prognosticator in the disposition for the effective and safe use of numerous drugs and xenobiotic compounds in humans.

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N‐acetylation phenotyping with dapsone in a mainland Chinese population.

Cited by 24 publications

References 21 publications

N‐acetylation polymorphism of dapsone in a Japanese population.

N‐acetylation polymorphism of dapsone in a Japanese population.

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Acetylation phenotype status in a Bangladeshi population and its comparison with that of other Asian population data

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