Ambulatory blood pressure monitoring can play an integral role in patient selection, dosage adjustment and efficacy assessment in clinical trials of antihypertensive agents.

OBJECTIVE: To evaluate the efficacy and duration of action of the angiotensin converting enzyme inhibitor quinapril hydrochloride by using ambulatory blood pressure monitoring. DESIGN: Eleven centers in the USA and Canada entered 155 patients with previously diagnosed hypertension into a 4-week placebo-baseline phase. Twenty patients (13%) with elevated diastolic blood pressure (DBP) only by cuff measurement were excluded from entry into a double-blind test based on ambulatory blood pressure monitoring, and 135 patients with a mean waking blood pressure of 155/100 mmHg were assigned randomly to receive either quinapril or placebo once a day for 8 weeks, with optional titration to a higher dose after 4 weeks, based on the DBP response assessed by repeat ambulatory blood pressure monitoring only. RESULTS: Quinapril therapy produced highly significant decrease in mean daytime DBP compared with placebo. The antihypertensive effect of quinapril was evident over 24 h, with 50% of the peak effect remaining at the trough. After 4 weeks of treatment 49% of the patients in the quinapril group were titrated to the higher dose compared with 86% of the patients who had been receiving placebo. More than 70% of the patients in the quinapril group who remained at the low dose would have been titrated to the higher dose based solely on the clinic DBP measurements. CONCLUSIONS: The use of ambulatory blood pressure monitoring in the present study reduced the false-positive response to placebo and lessened the likelihood of titrating patients to the higher dose of quinapril in comparison with the number that would have been so treated based on clinic blood pressure measurements alone. More importantly, our results suggest that the convenience, ease and relatively low cost of traditional cuff blood pressure measurement should be weighed against the potential shortcomings of the method.

Comparative mutagenicity of aliphatic epoxides in Salmonella.

37 aliphatic epoxides comprising 6 subclasses (unsubstituted aliphatic epoxides, halogenated aliphatic epoxides, glycidyl esters, glycidates, glycidyl ethers and diglycidyl ethers) were tested, under code, for mutagenicity in Salmonella strains TA98, TA100, TA1535 and TA1537 and/or TA97 with and without metabolic activation using a standardized protocol. The 4 halogenated aliphatic epoxides and the 4 diglycidyl ethers were all mutagenic. The 2 glycidates were negative in all strain/activation systems used while all 5 glycidyl esters were mutagenic. 3 of the 8 unsubstituted aliphatic epoxides and 11 of the 12 glycidyl ethers were mutagenic. Glycidol also was mutagenic whereas 9,10-epoxyoctadecanoic acid, 2-ethylhexyl ester was not mutagenic. Of the 28 mutagenic compounds, all but neodecanoic acid, 2,3-epoxypropyl ester and 2-ethylhexyl glycidyl ether were detected in TA100 without activation. The latter two were detected only with activation in TA100 and TA1535. The majority of the other 26 chemicals were also mutagenic in TA1535 without activation. Good intra- and interlaboratory reproducibility was seen in the results of each of the 4 chemicals tested in more than one set of experiments. The current results confirm and extend the observations of other investigators regarding structural effects on the mutagenicity of members of the aliphatic epoxide class of chemicals.