Comparative Bioavailability Study of Sparfloxacin Formulation

(1)

Abstract :

Department of Pharmacology,

Keimyung University School of Medicine, Daegu, Korea

(2)

(3)

(4)

Fig. 1. HPLC chromatograms of plasma samples. (A) blank plasma, (B) plasma spiked with internal standard, and (C)

plasma at 2 hr after 200 mg oral administration of Spara tablets.

(5)

Concentration ( g/mL)

Precision (CV%)

Within-day Between-day

Accuracy (%)

0.025 4.78 7.99 115.6

0.1 2.93 3.78 95.7

0.5 2.61 3.17 100.2

1 1.14 1.20 100.5

1.5 1.06 1.56 99.2

2 0.75 1.67 100.3

(6)

Fig. 2. Mean plasma concentration-time profiles of sparfloxacin in 26 healthy Korean volunteers after single oral administration of 200 mg of two sparfloxacin formulations. Date represented Mean SD.

Table 2. Comparison of sparfloxacin pharmacokinetic parameters after single oral administration of 200 mg of Spacin or Spara tablets

Pharmacokinetic parameters Spacin Spara

AUC

t

(ng hr/mL) 25562.7 8323.8 26440.3 7444.7

C

max

(ng/mL) 1021.5 338.5 1096.0 277.4

T

^max

(hr) 5.31 1.98 3.65 1.6

Half-life (hr) 18.43 3.56 18.02 2.55

(Mean SD, n=26)

Table 3. The mean and confidence intervals of the mean pharmacokinetic parameters of the test (Spacin tablet) and the reference preparation (Spara tablet)

AUC C

^max

T

^max

90% CI 0.8987 1.0177 0.8309 1.0007 19.8899 70.6364

Pharmacokinetic parameters

Test/Reference 0.956 0.911 BA Diff(%) 45.263

Detectable difference (%) 11.196 17.197 43.305

1- >0.9 0.894 <0.6

(7)

1. Kojima T, Inoue M, Mitsuhashi S. In vitro activity of AT-4140 against clinical bacterial isolates.

Antimicrob Agents Chemother 1989;33:1980-8.

2. Nakamura S, Minami A, Nakata K, Kurobe N, Kouno K, Sakaguchi Y, et al. In vitro and in vivo antibacterial activities of AT-4140, a new broad- spectrum quinolone. Antimicrob Agents Chemother 1989;33(8):1167-73.

3. Kojima T, Inoue M, Mitsuhashi S. In vitro activity of AT-4140 against quinolone- and methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 1990;34(6):1123-7.

4. Barry AL, Fuchs PC. In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin. Antimicrob Agents Chemother 1991;35(5):955-60.

5. Nakamura S, Kurobe N, Ohue T, Hashmoto M, Shimizu M. Pharmacokinetics of a novel quinolone, AT-4140, in animals. Antimicrob Agents Chemother 1990;34(1):89-93.

6. Miyamoto T, Matsumoto J, Chiba K, Egawa H, Shibamori K, Minamida A, et al. Synthesis and structure-activity relationships of 5-substituted 6,8 -difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency.

J Med Chem 1990;33(6):1645-56.

7. Montay G, Bruno R, Vergniol JC, Ebmeier M, Le Roux Y, Guimart C, et al. Pharmacokinetics of sparfloxacin in humans after single oral administration at doses of 200, 400, 600, and 800 mg.

J Clin Pharmacol 1994;34(11):1071-6.

8. Fillastre JP, Montay G, Bruno R, Etienne I, Dhib M, Vivier N, et al. Pharmacokinetics of sparfloxacin in patients with renal impairment. Antimicrob Agents Chemother 1994;38(4):733-7.

9. Lyon DJ, Cheung SW, Chan CY, Cheng AF. Rapid

HPLC assay of clinafloxacin, fleroxacin,

levofloxacin, sparfloxacin and tosufloxacin.

(8)

Monit 1999;21:411-5.

11. .

2002-60 , 2002. 11. 22.

12. Mody VD, Pandya KK, Satia MC, Modi IA, Modi RI, Gandhi TP. High performance thin-layer chromatographic method for the determination of

Pharmacokinet 1993;25:358-69.

14. Kamberi M, Kotegawa T, Tsutsumi K, Nakamura K, Nakano S. Sparfloxacin pharmacokinetics in healthy volunteers: the influence of acidification and alkalinization. Eur J Clin Pharmacol 1998;54:

633-7.