Differences in the single-oral-dose pharmacokinetics and urinary excretion of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects.

BACKGROUND AND OBJECTIVES: The present study was conducted to determine if ethnic differences exist for single oral dose pharmacokinetics of paracetamol and its conjugates between Hong Kong Chinese and Caucasian subjects. METHODS: Twenty healthy Chinese (n = 11) and Caucasian (n = 9) subjects, aged 21-44 years, 11 male and nine female, were given oral paracetamol syrup 20 mg/kg, following an overnight fast. Paracetamol and its metabolites (glucuronide, sulphate, cysteine and mercapturic acid conjugates) were measured in serial plasma samples (0.25, 0.5, 0.75, 1.0, 1.5, 2, 3,...,12, 24 h) and urine collections (0-24 h) by high-performance liquid chromatography. RESULTS: In Chinese subjects, the (mean range) peak plasma concentration of paracetamol was 23.8 mug/mL (17.9-32.3) and time to attain this peak 0.66 h (0.5-0.75). This was lower (P < 0.015) at 18.7 microg/mL (14.4-22.9) and achieved later (P < 0.033) at 1.06 h (0.5-2.0) in Caucasians. In Chinese subjects, plasma levels of glucuronide were lower, sulphate higher and cysteine conjugates significantly lower than in Caucasians (P < 0.05). Chinese subjects excreted 6% more sulphate and 5% less glucuronide. They also excreted significantly less mercapturic acid conjugates (P < 0.001). DISCUSSION AND CONCLUSION: Chinese subjects show more rapid absorption of paracetamol, a tendency to produce less glucuronide but more sulphate conjugates and reduced production of cysteine and mercapturic acid conjugates. The latter may help to protect against hepatotoxicity following paracetamol overdose.

Peripheral vascular disease in Type 2 diabetic Chinese patients: associations with metabolic indices, concomitant vascular disease and genetic factors.

AIMS: Conventional and genetic risk factors have been reported to play a role in the pathogenesis of vascular disease, but do not explain the lower burden of cardiac and peripheral vascular disease (PVD) in Chinese compared with Caucasians. The role of renin-angiotensin system (RAS) gene polymorphisms and conventional vascular risk factors has not been determined. METHODS: A total of 3097 Chinese diabetic subjects were screened for PVD, which was identified in 194 of the 2967 patients with Type 2 diabetes. Biochemical parameters and the genotype and allele frequencies of three RAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms were then compared between the PVD patients and 1046 age, gender and diabetes duration-matched patients without PVD. RESULTS: PVD identified in 6.5% was associated with significantly worse glycaemic control, lipid profile and renal function. Smoking was more common, as were the other macro- and microvascular diseases. The prevalence of hypertension was similar between the groups, yet diastolic blood pressure was slightly lower in the PVD group. The ACE D allele was significantly more frequent in patients with PVD compared with the matched diabetic controls (38.1 vs. 29.8%, P = 0.039). No differences in the AT1R or AGT polymorphisms were observed. CONCLUSIONS: PVD was associated with a worse metabolic profile and greater concomitant vascular disease than controls. The ACE I/D polymorphism was associated with PVD in these Type 2 diabetic patients.

Obesity and cardiovascular risk factors in Hong Kong Chinese.

The purpose of this cross-sectional study was to examine the risk associations between obesity indexes [body mass index (BMI) and waist circumference (WC)], cardiovascular risk factors [plasma glucose and lipids, blood pressure and urinary albumin excretion (UAE)] and morbidity conditions (Type 2 diabetes mellitus, hypertension, dyslipidaemia and/or albuminuria) in Hong Kong Chinese. Seven-hundred and two Hong Kong Chinese subjects (18-65 years of age, 59.4% of whom had at least one morbidity condition) were recruited from the Prince of Wales Hospital, Hong Kong SAR. The measurements taken of the subjects included: height; weight; waist and hip circumferences; blood pressure; fasting plasma glucose and lipids; and 24-h UAE. The mean BMI was 22.4 and 25.7 kg m(-2) in healthy subjects and patients, respectively. The mean WC measurements of healthy subjects and patients were 77.1 and 86.4 cm in males and 71.0 and 81.8 cm in females, respectively. There were increasing trends between obesity indexes and the severity of cardiovascular risk factors and the prevalence of morbidity conditions (all P-values for trend <0.05). Using 19.0-20.9 kg m(-2) and <70 cm as a referent, subjects with a BMI of > or =25.0 kg m(-2) (in both sexes) and/or a WC of > or =85 cm in males and > or =75 cm in females had an age-adjusted odds ratio between 3.2 and 4.4 for the occurrence of at least one morbidity condition. Patients with a greater number of comorbidities also had higher BMI and WC measurements (all P-values for the trend were <0.05 with adjustment for age and gender). Hence, despite Hong Kong Chinese being less obese than Caucasians, the intimate relationships among obesity, cardiovascular risk factors and morbidity conditions remain. Our data support using lower BMI and WC levels to define obesity and its associated health risks rather than using the criteria established from Caucasians who generally have larger body frames.