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Objective: Our objective was to evaluate ethnic differences in response to morphine and to determine whether any detectable differences were pharmacokinetically based., Methods: This cohort study was carried out in a teaching hospital. Sixty-six young, healthy male subjects from 3 ethnic groups (Caucasians, native Indians, and Latinos; n = 22 in each group) consented to participate. All subjects received an intravenous morphine bolus of 0.08 mg/kg followed by 0.002 mg/kg. min infused for 30 minutes. Respiratory response was evaluated with the carbon dioxide rebreathing method before and at 25, 95, 180, and 360 minutes after morphine administration. Vital signs and opioid side effects were recorded, and serial blood samples were analyzed for morphine, morphine-3-glucuronide, and morphine-6-glucuronide (M6G)., Results: All 3 groups had suppression of the ventilatory response to hypercapnia, but the degree of blunting of the ventilatory response differed among groups. Compared with Caucasians, native Indians had an additional 18% reduction in ventilatory response after morphine administration (95% confidence interval, -35% to -2%). The incidence of side effects was similar in all groups (P =.18). Caucasians had higher plasma levels of M6G than did native Indians or Latinos. M6G areas under 6-hour concentration-versus-time curve were as follows: Caucasians, 12,065 +/- 4354; native Indians, 8464 +/- 4809; and Latinos, 9156 +/- 3764 ng. min/mL (P =.03)., Conclusions: Ethnicity influences the response to morphine. Native Indians are more susceptible to morphine depression of the ventilatory response than Caucasians, despite the higher serum M6G levels in Caucasians.

This article reviews the data from drug utilisation research on antidiabetic agents, oral hypoglycaemics and insulin. Study methods specific to this type of pharmacoepidemiological research are discussed and critiqued. A brief overview of the sources of drug utilisation data is presented, followed by a review of specific pharmacoepidemiological investigations. We evaluate the usefulness of these studies in assessing true drug consumption, in evaluating comorbidity in diabetic patients and in measuring the prevalence of diabetes. International comparisons of antidiabetic drug utilisation, also reviewed and analysed, demonstrate wide variations in the use of hypoglycaemic agents, which have arisen for reasons which are unclear. Drug utilisation research thus far has been limited by the paucity of studies relating these variations in antidiabetic drug use to specific clinical outcomes. There is a need to expand the applications of research on the use of antidiabetic agents, including assessment of patterns of morbidity across geographic boundaries and over time.

Cancer of the bile ducts is rare and little is known about its risk factors. Recently, an association between methyldopa therapy and biliary carcinoma was reported in a retrospective case-control study. If this association were real, it would represent a significant health hazard, because methyldopa is widely prescribed. Using analysis of covariance to study the relationship between biliary tract cancer rates (obtained from 11 cancer registries in the US, Canada, Europe, and Asia) and per capita methyldopa sales (obtained from its manufacturer), this possible association was re-examined. For the rates of all biliary tract cancers combined, using both three- and ten-year lag periods between drug sales and disease, there were no associations between methyldopa and biliary carcinoma. When the rates for the biliary tract cancer sites were examined separately, one small positive regression coefficient was observed with extrahepatic biliary tract cancer, using the ten-year lag period only (p = 0.03). Since the majority of biliary tract cancers are extrahepatic in origin, it is likely that most of the cancers coded as 'biliary tract cancer, part unspecified' are actually extrahepatic. Also, the magnitude of the slope is very small, contrary to what one would expect with a common drug exposure and an uncommon disease. For these reasons, we believe that the negative results obtained with the combined rates for biliary tract cancer are more meaningful than the results obtained for each cancer site separately. In conclusion, our data do not support the presence of an association between methyldopa and biliary tract cancer.