Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: Stomatological preparations; Antiinfectives and antiseptics for local oral treatment.
ATC code: A01AB03.

General properties

Chlorhexidine digluconate is an antimicrobial agent active against a wide spectrum of Gram-positive and Gram-negative organisms, yeast, fungi, facultative anaerobes and aerobes. Chlorhexidine is predominately a “membrane-active” agent; it damages the outer membrane in the bacteria.
In an ex vivo study of plaque samples, taken from 25 patients with periodontal disease, exposure to escalating doses of chlorhexidine, resulted in elimination of 99% of subgingival bacteria at concentrations of 125 µg/mL or more. The MIC values for various oral cavity micro-organisms to chlorhexidine are tabulated below:

Micro-organisms                             MIC (µg/mL)
Porphyromonas gingivalis                    62
Prevotella intermedia                       62
Campylobacter concisus                      31
Capnocytophaga ochracea                     250
Hemophilus aphrophilus                      8
Streptococcus mutans                        8
Actinobacillus actinomycetemcomitans        62
Bacteroides forsythus                       125
Bacteroides melaninogenious                 62
Eikenella corrodens                         62
Streptococcus intermedia                    125
Streptococcus sanguis                       125
Veilonella parvule                          62
Bacteroides fragilis                        250
Capnocytophaga sp.                          500

Other information
Clinical microbiology studies with chlorhexidine mouthrinse have demonstrated the efficacy of chlorhexidine in reducing the numbers of periodontopathic bacteria, with a minimal risk of developing resistance. These studies, demonstrating the use of chlorhexidine for 6 months and up to 2 years, did not result in overgrowth of pathogenic bacteria or changes in the antimicrobial susceptibility of the oral flora.

Chlorhexidine resistance to bacteria usually results from either changes in the bacterial cell membrane, limiting chlorhexidine uptake, or low-level plasmid-encoded resistance. However, since neither of these mechanisms have been associated with the Bacteroides sp., major pathogens in periodontal pockets, and since the concentrations of chlorhexidine delivered by the PerioChip are relatively high, there is no concern about the development of chlorhexidine resistance following PerioChip administration.

PerioChip

In a 6-month study of the PerioChip, microbiological examination by DNA probe of bacteria from periodontal pockets, showed a sharp decrease in micro-organisms.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

In order to maintain a therapeutically effective concentration, PerioChip delivers a sustained release of chlorhexidine from the gelatin matrix of the periodontal insert over a period of seven days. This release is most rapid within the first 24 hours after periodontal insert placement with a peak concentration of about 2000 µg/mL at 2 hours, followed by a slow reduction in the concentration of chlorhexidine over a period of seven days. A microbiologically effective dose of at least 125 µg/mL is maintained during the release period.

There was no evidence of any systemic absorption following periodontal insert insertion. In addition, low systemic absorption of chlorhexidine has been demonstrated in studies conducted in animals and humans employing high oral doses of chlorhexidine.