Comparative pharmacokinetic and pharmacodynamic characteristics of amlodipine besylate and amlodipine nicotinate in healthy subjects.

BACKGROUND AND AIM: Amlodipine, a dihydropyridine calcium antagonist, is prescribed for the management of angina and hypertension, and is sold as amlodipine besylate. However, a new salt formulation, amlodipine nicotinate, has recently been developed. Here, we evaluated the comparative pharmacokinetic and pharmacodynamic characteristics of the nicotinate and besylate forms of amlodipine. SUBJECTS AND METHODS: A randomized, 2-way crossover study was conducted in 18 healthy male volunteers to compare the pharmacokinetics and pharmacodynamics of these two forms, i.e. amlodipine nicotinate (test) and amlodipine besylate (reference), after administration of a single dose of 5 mg of each drug and a washout period between doses of 4 weeks. Blood samples for the pharmacokinetic analysis of amlodipine were obtained over the 144-hour period after administration. Systolic and diastolic blood pressures and pulse rates were recorded immediately prior to each blood sampling. RESULTS: All participants completed both treatment periods, and no serious adverse events occurred during the study period. After administering a single dose of each formulation, mean AUC0-infinity and Cmax values were 190.91+/-60.49 ng x h/ml and 3.87+/-1.04 ng/ml for the test formulation and 203.15+/-52.05 ng x h/ml and 4.01+/-0.60 ng/ml for the reference formulation, respectively. The 90% confidence intervals of test/reference mean ratios for AUC0- infinity and Cmax fell within the predetermined equivalence range of 80 - 125%. Pharmacodynamic profiles including systolic and diastolic blood pressures and pulse rates exhibited no significant differences between the two formulations. CONCLUSION: The two amlodipine formulations showed similar pharmacokinetic and pharmacodynamic characteristics and the new amlodipine formulation, amlodipine nicotinate, was found to be equivalent for pharmacokinetics to the currently available amlodipine besylate with respect to the rate and extent of amlodipine absorption.

Maternal occupational exposure and congenital malformations.

A case-referent study was conducted to assess the risk of congenital malformations in relation to maternal occupational exposure before and during pregnancy. Three hundred and twenty-five cases of major malformations and 325 normal (at birth) referents identified in 15 maternity hospitals were included in the study. The occupational history obtained from an interview of the mother was blindly reviewed by an industrial hygienist who assessed the presence of chemical exposure and the probability of exposure. The results suggested that mothers of the case children with oral clefts were more often exposed to solvents during pregnancy [odds ratio (OR) 7.9, 90% confidence interval (90% CI) 1.8-44.9] and worked more often as cleaners (four cases, no referents). Digestive anomalies (OR 11.9, 90% CI 2.0-149) and multiple anomalies (OR 4.5, 90% CI 1.4-16.9) were also associated with occupational exposure to solvents at work. These results were not modified when differences in maternal age, area of residence, and socioeconomic status were taken into account.

Total synthesis of a demethoxy-egonol from Styrax obassia.

The total synthesis of a demethoxy-egonol isolated from Styrax obassia, 5-(3-hydroxypropyl)-2-(3',4'-methylenedioxyphenyl)benzofuran (9), is described. The key steps involve the construction of a 2-arylbenzofuran skeleton 7 from methyl 3-(4-hydroxyphenyl)propionate with 2-chloro-2-methylthio-(3',4'-methylenedioxy)acetophenone (6) in the presence of ZnCl2 and successive desulfurization of the resulting product 7.

Agent orange and the risk of gestational trophoblastic disease in Vietnam.

There have been claims of an increased risk for gestational trophoblastic disease (i.e., hydatidiform mole and choriocarcinoma) in Vietnam since the period of Agent Orange sprayings. In 1990, we conducted a case-control study in Ho Chi Minh City to investigate risk factors for gestational trophoblastic disease in Vietnam. Eighty-seven married women, all of whom had a recent pathologic diagnosis of gestational trophoblastic disease, identified in the Obstetrical and Gynecological Hospital, were included in the study. Eighty-seven married women who were admitted mainly in the surgery departments of the same hospital were the controls, and they were matched to cases for age and area of residence. Odds ratios (ORs), adjusted for matching variables and other potential confounders, were estimated with unconditional logistic regression. A statistically significant trend in risk was observed with previous live births (p = .01). Cases were found to eat less meat per wk (OR = 0.4, 95% confidence interval [95% CI] = 0.2-0.9 for > or = five meat dishes) and to own fewer consumer goods than controls. An increase in risk was associated with the breeding of pigs (OR = 5.7, 95% CI = 1.2-27.6 for raising three or more pigs). A cumulative Agent Orange exposure index was constructed, using the patient's complete residence history. No significant difference was found between cases and controls for this index (OR = 0.7, 95% CI = 0.2-1.8 for high-exposure category), nor was such a difference noted for the agricultural use of pesticides.

Congenital malformation and maternal occupational exposure to glycol ethers. Occupational Exposure and Congenital Malformations Working Group.

Glycol ethers are found in a wide range of domestic and industrial products, many of which are used in women's work environments. Motivated by concern about their potential reproductive toxicity, we have evaluated the risk of congenital malformations related to glycol ether exposure during pregnancy as part of a multicenter case-control study, conducted in six regions in Europe. The study comprised 984 cases of major congenital malformations and 1,134 controls matched for place and date of birth. Interviews of the mothers provided information about occupation during pregnancy, sociodemographic variables, and other potential risk factors (medical history, tobacco, alcohol, drugs). A chemist specializing in glycol ethers evaluated exposure during pregnancy, using the job description given by the mother, without knowledge of case or control status. We classified malformations into 22 subgroups. The overall odds ratio (OR) of congenital malformation associated with glycol ether exposure was 1.44 [95% confidence interval (CI) = 1.10-1.90], after adjustment for several potential confounders. The association with exposure to glycol ethers appeared particularly strong in three subgroups: neural tube defects (OR = 1.94; 95% CI = 1.16-3.24), multiple anomalies (OR = 2.00; 95% CI = 1.24-3.23), and cleft lip (OR = 2.03; 95% CI = 1.11-3.73). In this last subgroup, risk, especially of an isolated defect, tended to increase with level of exposure.