Pharmacokinetics and clinical efficacy of delmopinol in an open rinse time study in healthy volunteers.

Purpose: To compare three different rinse times with delmopinol (15, 30 and 60 seconds) with respect to inhibition of plaque growth and to determine the pharmacokinetic parameters of delmopinol for these rinse times. Methods: This open and randomized study with a cross-over design was performed in healthy male volunteers and consisted of four treatment periods of 1 week separated by washout periods of at least 6 days. The first test period started with staining of the teeth followed by planimetric recordings before and after professional cleaning. Adverse records were also obtained. The volunteers, randomly assigned to a rinsing time sequence, were instructed to cease all oral hygiene measures except for the mouthrinse with placebo or delmopinol solutions. The rinses were performed without supervision twice daily for 7 days for each rinsing time. On Day 7, plaque % index and planimetric registrations were obtained, adverse effects recorded and the teeth were cleaned professionally. Plasma samples for the pharmacokinetic evaluation were also taken. The remaining test periods were performed in the same way, except that no baseline planimetric recordings were made. During the washout periods the volunteers returned to their normal oral hygiene behavior. Venous blood samples were drawn from all volunteers into sodium heparin-containing tubes. Results: A significant time-response was obtained with respect to the planimetric results. The mean areas of the teeth covered with plaque after the test periods (placebo, 15, 30 and 60 seconds) were 41%, 29%, 23% and 18%, respectively. Statistical analysis showed that rinsing with delmopinol for 30 or 60 seconds differed significantly (P< 0.05) from placebo. There was also a significant difference between rinsing for 15 and 60 seconds. From the plaque % index data it was found that all three rinsing times differed significantly from placebo. However, between the three rinse times with active solution, no significant difference in plaque % index occurred. Statistical analysis of the systemic exposure, in terms of the pharmacokinetic parameters AUC(12h) and C(max) showed a significant treatment effect. The exposure increased with increasing rinse time, although the increase (AUC(12h) and C(max)) was less than proportional to the rinse time.