Comparison of the pharmacokinetics of three-day and five-day regimens of azithromycin in plasma and urine

Abstract

In an open crossover study, the pharmacokinetics of three-day and five-day regimens of azithromycin were compared. Fourteen healthy volunteers received oral doses of azithromycin once-daily, over three days (500 mg/day) and over five days (500 mg on day 1, followed by 250 mg/day on days 2-5). Plasma and urine concentrations were determined by HPLC. Azithromycin was found to be absorbed rapidly on the first and the last days of both regimens, with mean Tmax ranging between 2.5-3 h. On day 1, peak plasma concentrations were 0.37 mg/L and 0.31 mg/L, respectively, with three- and five-day regimens, and increased to 0.42 mg/L on the last day of the three-day regimen, but decreased to 0.18 mg/L at the end of the five-day regimen. Similarly, the AUC0-24 increased from 1.30 to 1.88 h.mg/L during the three-day regimen, and decreased from 1.24 to 0.80 h.mg/L on the five-day regimen. After absorption, azithromycin was distributed rapidly; the respective half-lives were 2.4 h and 2.2 h with the three-day and five-day regimens. Thereafter, a polyphasic decline of plasma concentrations was observed; the average half-lives between 8-48 h after administration were 27.9 h (three-day regimen) and 35.8 h (five-day regimen). In urine, 5.5% (three-day regimen) and 4.6% (five-day regimen) of the total dose was found as unchanged azithromycin over a 12-day period. The observed pharmacokinetics of azithromycin with both regimens conformed with the known pharmacokinetic behaviour of the drug. The treatment-related differences seen in the plasma concentrations were as expected from the different dosage schedules.

Bioequivalence assessment of Azomycin® (Julphar, UAE) as compared to Zithromax® (Pfizer, USA)—two brands of azithromycin—in healthy human volunteers

“…The mean concentration -time profiles for the two formulations of the two dosage forms are shown in Figures 1 and 2 for azithromycin capsules and suspension, respectively. All calculated pharmacokinetic parameter values were in good agreement with the previously reported values [5,[9][10][11][12][13][14][15][16][17][18]. According to published data, the oral bioavailability of azithromycin is around 37% [5,[10][11][12].…”

“…The elimination half-life was reported to be 68 h and is prolonged because of extensive tissue sequestration and binding [17]. The elimination of azithromycin from serum is biphasic, exhibiting a short tissue distribution phase followed by a longer elimination phase [12,18]. The terminal elimination half-life is determined by the movement of azithromycin from distribution sites [12].…”

Physiologically-Based IVIVC of Azithromycin

“…This was due to inclusion of permeability factor along with IVIVC, which is not the case in in-vitro profile as per USP method. It is worthwhile noting that azithromycin bioavailability reached around 60%, which is in agreement with literature value of 57% [2]. Moreover, Figure 2 clearly showed that In-vitro and IVIVC dissolution profiles are strongly correlated (R=1).…”

“…The half-life of elimination of azithromycin has been reported to be variable and can reach 70 hours, which is partially explained by its extensive tissue uptake and slow tissue release. The disposition of azithromycin from serum is a biphasic process, exhibiting a short tissue distribution phase followed by a longer elimination phase [2,3,4,5]. Azithromycin appears to demonstrate a time-dependent versus time-accumulation profile in breast milk [6].…”

Pharmacokinetics of macrolides. Comparison of plasma, tissue and free concentrations with special reference to roxithromycin

“…Because of their higher stability in acidic environments and prolonged elimination half-lives, the new macrolides azithromycin [1], clarithromycin [2], and roxithromycin [3] all show pharmacokinetic characteristics superior to those of erythromycin [3]. This means that more favourable dosage regimens can be applied [4,5].…”