Evaluation of gatifloxacin penetration into skeletal muscle and lung by microdialysis in rats.
This study aimed to investigate gatifloxacin distribution into skeletal muscle and lung interstitial fluid by microdialysis and to correlate free tissue and free plasma levels of the drug. Microdialysis recoveries were determined in vitro by extraction efficiency and retrodialysis at 80, 160 and 400 ng/ml resulting in 33.5+/-1.3%, 33.1+/-1.2%, 31.8+/-2.7% and 31.4+/-2.6%, 33.1+/-2.2%, 30.6+/-3.3%, respectively. In vivo recovery by retrodialysis in Wistar rats' skeletal muscle and lung were 29.1+/-1.0% and 30.7+/-1.4%, respectively. The recovery was constant and independent on the method or media used. Gatifloxacin tissue penetration was investigated after intravenous dosing of 6 mg/kg to Wistar rats. Free skeletal muscle, lung and plasma profiles were virtually superimposable resulting in similar area under the curve (AUC(0-9)) of 3888+/-734 ng h/ml, 4138+/-1071 ng h/ml and 3805+/-577 ng h/ml, respectively (alpha=0.05). The tissue distribution factors were 1.02 and 1.08 for muscle and lung relative to plasma. In conclusion, free plasma levels are a good surrogate for gatifloxacin active levels at the infection site.
Tasso
Leandro
L
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre, RS, Brazil.
Bettoni
Clarissa C
CC
Oliveira
Laura K
LK
Dalla Costa
Teresa
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077734:Gatifloxacin; D008168:Lung / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D012997:Solvents; D000077734:Gatifloxacin