Distribution of systemic ciprofloxacin and doxycycline to gingiva and gingival crevicular fluid.
BACKGROUND
Systemic fluoroquinolones and tetracyclines reach steady-state levels in gingival crevicular fluid (GCF) that are several-fold higher than their levels in serum. The mechanism by which this occurs is unclear, but gingival fibroblasts are known to accumulate these agents. Uptake by fibroblasts could enhance their distribution to gingiva. To test this hypothesis, steady-state levels of these agents were assayed in serum, gingival connective tissue (GCT), and GCF.


METHODS
Healthy subjects who needed resective periodontal surgery participated in the study. Approximately 78 hours prior to the surgical appointment, each subject began a 3-day regimen of ciprofloxacin or doxycycline. At the surgical appointment (scheduled approximately 6 hours after the last dose), samples of blood and GCT were collected. GCF samples were collected on paper strips and measured with an electronic device. Samples were extracted and analyzed by high performance liquid chromatography.


RESULTS
Mean ciprofloxacin levels in serum, GCT, and GCF were 0.40 microg/ml, 1.38 microg/g, and 1.66 microg/ml, respectively (P<0.001, N=9). For doxycycline, these levels were 1.11 microg/ml, 2.03 microg/g, and 2.41 microg/ml, respectively (P=0.002, N=8). For both agents, the GCT and GCF levels were significantly higher than serum levels (P<0.05), but not significantly different from each other.


CONCLUSIONS
Our findings suggest that fibroblasts could play an important role in the distribution of fluoroquinolones and tetracyclines to the gingiva. By accumulating these agents in GCT, fibroblasts could contribute to the relatively high levels they attain in GCF.
Lavda
Maria
M
Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, OH 43218-2357, USA.
Clausnitzer
C Esther
CE
Walters
John D
JD
D000284:Administration, Oral; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004318:Doxycycline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005347:Fibroblasts / Q000378:metabolism*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D005883:Gingival Crevicular Fluid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013754:Tetracyclines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D013754:Tetracyclines; D002939:Ciprofloxacin; D004318:Doxycycline
Science. 1999 May 21;284(5418):1318-22
10334980
J Clin Periodontol. 2000 Jan;27(1):53-60
10674962
J Periodontol. 2000 Sep;71(9):1448-52
11022774
Oral Microbiol Immunol. 2002 Oct;17(5):267-71
12354206
J Dent Res. 2002 Dec;81(12):836-40
12454098
Antimicrob Agents Chemother. 1992 Dec;36(12):2634-8
1482130
J Clin Pharm Ther. 1992 Apr;17(2):111-5
1583077
J Periodontol. 1996 Mar;67 Suppl 3S:291-297
29539842
J Periodontol. 1987 Aug;58(8):529-39
3305856
J Clin Periodontol. 1986 Oct;13(9):841-4
3537018
Antimicrob Agents Chemother. 1980 Feb;17(2):193-8
6247968
J Periodontol. 1980 Sep;51(9):530-4
6999148
J Clin Periodontol. 1981 Apr;8(2):117-21
7019267
J Clin Periodontol. 1981 Aug;8(4):359-67
7033302
Infect Immun. 1995 Oct;63(10):3878-85
7558295
Scand J Dent Res. 1993 Oct;101(5):299-303
8248732
J Periodontal Res. 1996 Aug;31(6):441-3
8884638
J Pharm Biomed Anal. 1997 Sep;16(1):111-7
9447558
Periodontol 2000. 1997 Feb;13:91-120
9567925
Periodontol 2000. 1996 Feb;10:45-78
9567937