No abstract

Intravenous administration of amlodipine (single dose, 10 mg) to 12 volunteers gave a mean plasma half-life of 34 h, mean clearance of 7 ml min'1 kg-' and a mean apparent volume of distribution of 21 1 kg-'. 2 Oral administration (single dose, 10 mg) to the same 12 volunteers gave a mean systemic availability of 64% and a mean plasma half-life of 36 h. 3 In a second study, repeated oral administration (once daily for 14 days, 15 mg) to 28 volunteers resulted in steady state plasma drug concentration being reached after seven doses, an accumulation of approximately threefold and a mean half-life of 45 h.

The removal of plaque by toothbrushing with toothpaste is the most common form of plaque control in the developed world. However, the use of chemical adjuncts such as mouthrinses is increasing. In practice mouthrinses and toothpaste are used together, however, in many clinical trials, employed to assess mouthrinse activity, toothpaste use is suspended. This fails to measure the effect of chemical interactions which are known to occur between toothpaste ingredients and mouthrinses. The objective of this trial was to develop a methodology which would assess the adjunctive chemical plaque inhibitory action of mouthrinses, when used with toothpaste but without the indeterminate variable of toothbrushing. The study was a single blind, randomised, 7-way crossover design, based on a variation of a 4 day plaque regrowth model. The 2 x daily rinsing regimens produced increasing plaque scores in the following order: (1) water/chlorhexidine, (2) chlorhexidine/water, (3) chlorhexidine/toothpaste slurry, (4) toothpaste slurry/chlorhexidine, (5) water/toothpaste slurry, (6) toothpaste slurry/water, (7) water/water. Chlorhexidine and water or chlorhexidine and toothpaste slurry combinations produced significantly lower plaque scores than water alone. Slurry and water combinations resulted in less plaque than water alone, but differences were not significant. Toothpaste slurry and chlorhexidine produced significantly increased plaque scores compared to chlorhexidine and water. The study suggests that, outside the Hawthorne effect, chlorhexidine rinses would be less effective in reducing plaque when used with toothpaste than when used alone. The methodology could be employed as a screening tool for the evaluation of mouthrinses expected to be used as adjuncts to normal oral hygiene methods. The same could be used to optimise oral hygiene regimens which include the use of mouthrinses.

1 The metabolic fate of doxazosin was investigated in man, mouse, rat and dog using 14C-labelled compound. Bioavailability and pharmacokinetic studies were also conducted with nonlabelled drug, using a specific h.p.l.c. method. 2 Following both oral and intravenous administration, the major route of elimination of drugrelated compounds was via the faeces for all species studied. Comparison of the oral and intravenous data show that doxazosin is completely absorbed in man, mouse and rat and is moderately well absorbed in dog. 3 The drug is extensively metabolized, e.g. only about 5 % of the dose was excreted unchanged in man. Metabolism in man mainly involves 6-and 7-O-demethylation and 6' and 7'-hydroxylation. These and some minor products were common to the mouse, rat or dog and man.4 Plasma protein binding was high in all species studied, ranging from 95.3 % in the rat to 98.3 % in human patients. 5 Oral bioavailability is 60% in dog and approximately 50% in the rat, which is similar to the value of 63 % reported for man at therapeutic doses. Mean plasma clearance values were 13 ml min-' kg-' (dogs), 30 ml min-' kg-' (rats) and 1.2 ml min-' kg-' (human subjects). Mean plasma half-life values were 5 h in dogs and 1.2 h in rats: a value of 9 h was reported for human volunteers (cf. 2.5 h for prazosin). The long plasma half-life of doxazosin provides the basis for once-daily dosing.

Several triclosan and stannous fluoride toothpastes have been shown to have plaque inhibitory and more particularly gingival health benefits when compared to minus active controls. There have been relatively few studies to compare such products with conventional fluoride toothpastes in home use. The aim of this study was to compare the relative gingival health benefits of a triclosan/zinc citrate, triclosan/copolymer, stannous fluoride and conventional fluoride toothpastes in a home use study. The study was a double blind, parallel design with a total 143 healthy dentate volunteers (41 male, 102 female) who toothbrushed 2x daily with 1 of 4 toothpastes over an 18 week period. At the beginning of the trial, each volunteer was scored for plaque and gingivitis and then received a thorough prophylaxis. Each volunteer was allocated a toothpaste according to a predetermined randomisation scheme. The volunteers were then re-examined after 6, 12 and 18 weeks. No other oral hygiene products were used during this period. The results showed no statistically significant treatment differences between products for the gingival index throughout the 18 week-trial. No statistically significant treatment effects between products for plaque index were found at 6 or 18 weeks. However, a small but statistically significant treatment effect for plaque index was seen at 12 weeks in favour of the triclosan/copolymer toothpaste compared to the stannous fluoride and conventional fluoride toothpastes, this difference had disappeared by the 18 week examination. All volunteers oral hygiene and gingivitis scores improved after the baseline examination, and this improvement continued throughout the trial. This is a feature of nearly all toothbrushing studies and can be attributed to the initial prophylaxis and the Hawthorne phenomenon. Such phenomena, noted in home use clinical trials, may mask the efficacy of proven antiplaque formulations.