Concentration of 3 tetracyclines in plasma, gingival crevice fluid and saliva.
BACKGROUND
Systemically-administered tetracyclines have been used widely for treatment of periodontal diseases with little understanding of their delivery characteristics to periodontal tissues. This study was designed to measure concentrations of 3 tetracyclines in gingival crevice fluid (GCF), plasma and saliva of following systemic administration.


METHODS
The concentration of tetracycline (TC), minocycline (MN) and doxycycline (DX) was measured in gingival crevice fluid (GCF), plasma and saliva of 20 subjects following single sequential standard oral systemic doses. Gingival crevice fluid concentration was measured at 4 sites (2 shallow and 2 deep) before administration, and at 1 h and 2 h following administration. Plasma and saliva concentrations were measured from in samples at the same time points. No antibacterial activity was detected before administration. The highest concentrations were measured 2 h after administration.


RESULTS
The average concentrations at 2 h were highest in plasma (TC = 1.02, MN=2.18, DX=2.35 microg/ml). Intermediate concentrations were measured in GCF (TC=0.61, MN= 1.49, DX= 1.65 microg/ml). Saliva concentrations (TC=0.09 MN=0.31, DX=0.47 microg/ml) were the lowest of the 3 fluids monitored. Data are presented indicating that the average GCF concentration of systemically administered tetracyclines is less than the that of plasma concentration. The concentration of tetracyclines in GCF was strongly associated with plasma concentration, indicating a primary role of drug absorption in the delivery of these systemically administered antibiotics to the site of action in periodontal therapy. The average GCF concentration in individuals varied widely (between 0 and 8 microg/ml) with approximately 50% of samples not achieving levels of 1 microg/ml.


CONCLUSIONS
These observations suggest that poor absorption of orally-administered tetracyclines in many individuals may account for much of the variability in clinical response to antibiotics observed in practice.
Sakellari
D
D
Department of Periotontology, Dental School, Aristotelian University of Thessaloniki, Greece.
Goodson
J M
JM
Kolokotronis
A
A
Konstantinidis
A
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D004318:Doxycycline / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D010512:Periodontal Index; D010518:Periodontitis / Q000188:drug therapy*; D012463:Saliva / Q000737:chemistry; D013752:Tetracycline / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D013754:Tetracyclines / Q000008:administration & dosage* / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors
D000900:Anti-Bacterial Agents; D013754:Tetracyclines; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline