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Pharmacokinetic-pharmacodynamic analysis of azithromycin extended release in Japanese patients with common respiratory tract infectious disease.

AbstractOBJECTIVES:
it is known that the efficacy of azithromycin, in animal infection models, is best correlated with AUC/MIC. The pharmacokinetic-pharmacodynamic (PK-PD) relationship for azithromycin, however, has not been previously confirmed with clinical data. The objectives of this PK-PD analysis were to characterize exposure-response relationships for the efficacy and safety of azithromycin extended release (ER) in Japanese patients, and to evaluate the effects of potential covariates on the prediction of response.
METHODS:
sparse serum azithromycin concentration, MIC, efficacy and safety data were collected from three Japanese Phase 3 studies of a 2 g single dose of azithromycin-ER for respiratory tract infections. These sparse concentration data were combined with data from eight Phase 1 PK studies in Japanese and Western populations, to develop a robust population PK model using a non-linear mixed effects approach. The exposure-response relationships for efficacy and safety were evaluated using logistic regression.
RESULTS:
a two-compartment model with first-order absorption and first-order elimination with a lag time adequately described the PK of azithromycin-ER, without any significant ethnic differences in AUC. The percentage of bacteriological and clinical success in patients with AUC/MIC β€Š>β€Š 5 (95.8% and 100%, respectively) was much higher than in those with AUC/MICβ€Š ≤β€Š 5 (60.0% and 83.3%, respectively).
CONCLUSIONS:
as expected, the probabilities of success in the clinical and bacteriological responses were positively associated with AUC/MIC, but not with AUC. For the exposure-safety relationship, the incidence of treatment-related diarrhoea was inversely associated with azithromycin exposure.
AuthorsChieko Muto, Ping Liu, Koji Chiba, Toshio Suwa
JournalThe Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 66 Issue 1 Pg. 165-74 (Jan 2011) ISSN: 1460-2091 [Electronic] England
PMID21059616 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Azithromycin
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents (administration & dosage, adverse effects, pharmacokinetics)
  • Asian People
  • Azithromycin (administration & dosage, adverse effects, pharmacokinetics)
  • Bacteria (drug effects)
  • Bacterial Infections (drug therapy)
  • Diarrhea (chemically induced)
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Respiratory Tract Infections (drug therapy)
  • Serum (chemistry)
  • Young Adult

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