Abstract | OBJECTIVES: 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>β 5 (95.8% and 100%, respectively) was much higher than in those with AUC/MICβ ≤β 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.
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Authors | Chieko Muto, Ping Liu, Koji Chiba, Toshio Suwa |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 66
Issue 1
Pg. 165-74
(Jan 2011)
ISSN: 1460-2091 [Electronic] England |
PMID | 21059616
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Azithromycin
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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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