A clinical and microbiological study on the enantiomers of delmopinol

Abstract

Objective The clinical part of this study aimed to investigate whether the racemate of delmopinol [(±)-delmopinol] is equivalent to its two enantiomers [(+)-delmopinol and (−)-delmopinol] with respect to efficiency and to determine and compare their pharmacokinetic properties. The purpose of the pre-clinical part was to elucidate possible differences in antimicrobial efficiency. Materials and methods The compounds were tested clinically in a double-blind, randomized, cross-over study comprising three treatment periods of 4 days each. The antimicrobial efficacy of the enantiomers was compared in vitro with respect to planktonic and biofilm bacteria of different species. Results No statistically significant differences in prevention of plaque formation were observed. Except for a somewhat higher systemic exposure in terms of AUC and C_max indicated for (−)-delmopinol compared to (+)-delmopinol, the pharmacokinetic properties were similar. The most common adverse event was a transient anaesthetic feeling in the mouth. This event was reported with the same frequency for all three test solutions. The enantiomers showed similar antimicrobial effects on planktonic bacteria and their biofilms. Conclusions The enantiomers were found to be equally effective with respect to inhibition of plaque development and only minor differences were observed with respect to their pharmacokinetic properties. No differences could be observed in the adverse events reports. There is, therefore, no reason to use one of the enantiomers of delmopinol instead of the racemate. This was further supported by the antimicrobial tests. It is suggested that the combined action of cationic and neutral delmopinol is important for its effect on biofilms.

Keywords:

• Antibacterial effects
• biofilm
• clinical effect
• dental plaque
• pharmacokinetics

Acknowledgements

The authors thank Dr Ulrika Troedsson for valuable comments on the manuscript.

Disclosure statement

The clinical part of this study was financed by Biosurface AB, Malmö, Sweden, and was performed at the Dental Faculty, Malmö University, with KN as Investigator. At the time of the study TS (Study Director) and MÅ (Statistician) were employees at Biosurface AB, and BS (Supervisor, pharmacokinetics) held a position at the Department of Preclinical Development, Pharmacia AB, Helsingborg, Sweden. CB was engaged as a consulting pharmacokineticist at Kineticon AB, Uppsala, Sweden. The present address for CB is at the Medical Products Agency, Uppsala, Sweden. The authors otherwise have no financial or other direct association with the now manufacturer of the delmopinol 0.2% mouthrinse (Sinclair IS Pharma PLC, London, UK).