title: A PK/PD approach on the effects of clarithromycin against oral and nasal microbiota of healthy volunteers.
abstract: 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.
authors.affiliation: Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Del Bortolo Ruenis
authors.forename: G C
authors.initials: GC
authors.lastname: Nobre Franco
authors.forename: S
authors.initials: S
authors.lastname: Baglie
authors.forename: R H
authors.initials: RH
authors.lastname: Lopes Motta
authors.forename: R P
authors.initials: RP
authors.lastname: Simões
authors.forename: P L
authors.initials: PL
authors.lastname: Rosalen
authors.forename: L M
authors.initials: LM
authors.lastname: Franco
authors.forename: R A
authors.initials: RA
authors.lastname: Moreno
authors.forename: E
authors.initials: E
authors.lastname: Abib
authors.forename: F C
authors.initials: FC
authors.lastname: Groppo
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin