Pharmacokinetics of azithromycin in serum after administration of extended-release and immediate-release formulations in paediatric patients with acute otitis media

Abstract number: P1589

Fang A., Liu P., LaBadie R., Crownover P., Arguedas A.

Objectives: A 30 mg/kg single dose of AZ-IR has been used in paediatrics to treat AOM. AZ-ER formulation provides higher dose in one administration and has been used in adults. To provide exposure bridging between the two formulations, this study was to determine whether a 60 mg/kg single dose of ER provides similar or greater AZ systemic exposure compared to the 30 mg/kg IR in paediatric patients with AOM, by demonstrating that the lower boundary of the 90% confidence interval (CI) of the primary endpoint (ER/IR ratio of area under the curve over 72 hours AUC72) and the secondary endpoint (point-to-point concentration ratios) are geqslant R: gt-or-equal, slanted80% and geqslant R: gt-or-equal, slanted70% respectively.

Methods: This was a randomized open-label single-centre study. Thirty-eight AOM patients (6 months to 6 years old) received a single dose of AZ-ER 60 mg/kg or AZ-IR 30 mg/kg (n = 19 per group). Serum samples were collected at 1, 2, 3, 4, 8, 24, 48 and 72 hours after dosing. AZ levels were analyzed by validated HPLC/MS/MS method. PK analysis was done by non-compartmental method. Log transformed PK data were analyzed by one-way analysis of variance.

Results: Thirty-six Hispanic patients completed the study (61% male). Summary statistics of the PK parameters and concentrations at each time point are shown in the table.

•Primary Comparison of PK parameters: The ratio of the adjusted mean AUC72 (ER/IR) was 157.98% with the lower boundary of the 90% CI >80%.

•Secondary Comparisons of concentrations: The lower boundaries of the 90% CIs of ER/IR AZ concentration ratios for the first 3 hours were <70%, which was expected for ER formulation since it was designed to slow down the absorption (delayed Tmax and lower Cmax) to improve the tolerability. AZ ER concentrations at all remaining time points after 3 hours were higher than those from IR with the lower boundary of the 90% CI >70%.

•Safety: No serious adverse events or clinically significant safety labs other than from AOM were observed.

Conclusions: AZ-ER 60 mg/kg single dose provides similar or greater systemic exposure in paediatrics compared with the AZ-IR 30 mg/kg single dose. Both ER and IR were well tolerated.

PK endpointAdjusted geometric mean  
 AZ-ER N = 18AZ-IR N = 18ER/IR Ratio of adjusted means (%)90% confidence interval for ratio (%)
  AUC72 (ng·h/mL)98486234157.98(98.87, 252.44)
  Cmax (ng/mL)611.5667.391.63(56.21, 149.38)
  Tmax (h)*3 (2–8)2 (1–4)N/AN/A
Concentration (ng/mL)    
  C1100.0152.865.44(23.56, 181.77)
  C2293.1579.750.57(25.24, 101.30)
  C3382.0381.7100.07(57.91, 172.92)
  C4441.8267.9164.93(103.78, 262.12)
  C8244.8140.3174.41(110.07, 276.36)
  C24142.482.3173.01(111.45, 268.55)
  C4894.850.1189.35(129.76, 276.30)
  C7256.030.6183.14(124.61, 269.14)
AUC72: area under the curve over 72 hours; Cmax: the maximum concentration; Tmax: the time to reach Cmax; N/A: not applicable; *: median (range).

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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