A PK/PD approach on the effects of clarithromycin against oral and nasal microbiota of healthy volunteers.
OBJECTIVE
To assess the pharmacokinetics of clarithromycin (CLR) and its effects on oral and nasal microbiota in healthy volunteers in an open, randomized, two-period crossover design.


METHODS
A single 500 mg oral dose of CLR (Group 1: Merck; Group 2: Klaricid) was administered observing a 1-week interval between doses. Blood samples were collected from pre-dose to 24 h. Plasmatic concentrations of CLR were quantified by the LC-MS-MS method. Saliva and nasal mucosa swabs were obtained previously and after 1.33, 2, 6 and 12 h of drug administration. Pharmacokinetics and PK/PD (t > MIC, %t > MIC and AUC0-24/MIC ratio) parameters were estimated. The microorganism counts were obtained on different culture media.


RESULTS
No statistically significant differences were observed between the two formulations (p > 0.05) regarding the pharmacokinetic parameters. Total microorganisms, staphylococci and streptococci counts did not show statistical differences (p > 0.05) between the two groups during each sampling time. Considering the microorganisms of each group, no statistically significant differences were found after drug administration, but all differed from pre-dose counts (p < 0.05). The observed t > MIC ranged from 14.45 h (+/- 1.69) to 1.19 h (+/- 2.17) considering MICs of 0.25 microg/ml and 2.0 microg/ml, respectively. There was no correlation between any t > MIC, %t > MIC or AUC0-24 and bacterial reduction (between 0- and 12-h periods). However, the profile of reduction of microorganisms in both saliva and nasal samples were compatible with high values of t > MIC verified for both clarithromycin formulations.


CONCLUSIONS
Both formulations of clarithromycin had similar pharmacokinetics and efficacy.
Del Bortolo Ruenis
A P
AP
Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil.
Nobre Franco
G C
GC
Baglie
S
S
Lopes Motta
R H
RH
Simões
R P
RP
Rosalen
P L
PL
Franco
L M
LM
Moreno
R A
RA
Abib
E
E
Groppo
F C
FC
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002853:Chromatography, Liquid; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009296:Nasal Cavity / Q000382:microbiology*; D012463:Saliva / Q000382:microbiology*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017291:Clarithromycin