title: Pharmacodynamics of doxycycline for chemoprophylaxis of Lyme disease: preliminary findings and possible implications for other antimicrobials.
abstract: The purpose of this study was to begin to characterise the pharmacodynamic parameters of single-dose doxycycline for the prevention of Lyme disease following a tick bite. Based on limited data from published human and murine studies, it was found that there is a direct correlation between efficacy rate and the area under the time-concentration of free antibiotic curve divided by the minimum inhibitory concentration (fAUC/MIC) (R(2)=0.74, using Pearson correlation), but not the maximum concentration of free drug in serum divided by the MIC (fC(max)/MIC) or the time that the free drug concentration remains above the MIC (fT>MIC). To determine the possible implications of these findings for other antimicrobials, it was assumed that the pharmacodynamic properties of doxycycline would be pertinent to azithromycin, an antibiotic whose activity is known to correlate with AUC/MIC. By making such an extrapolation and using pharmacokinetic modelling with conservative assumptions on MIC values against Borrelia burgdorferi, it is hypothesised that a single 500 mg dose of azithromycin in humans should have comparable efficacy to doxycycline for the prevention of Lyme disease. Additional experimental studies are needed to clarify more precisely the pharmacodynamic properties of doxycycline and to validate the accuracy of this hypothesis.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. jooyun.lee@mssm.edu
authors.forename: Jooyun
authors.initials: J
authors.lastname: Lee
authors.forename: Gary P
authors.initials: GP
authors.lastname: Wormser
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D017963:Azithromycin / Q000493:pharmacokinetics / Q000494:pharmacology; D025065:Borrelia burgdorferi / Q000187:drug effects*; D018890:Chemoprevention / Q000379:methods*; D004318:Doxycycline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D008193:Lyme Disease / Q000517:prevention & control*; D051379:Mice; D008826:Microbial Sensitivity Tests; D044967:Serum / Q000737:chemistry; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin; D004318:Doxycycline