Experimental Study of Biliary Excretion of an Antibiotics with Changes in Bile-Duct Pressure

Koji Nakata, Hiroaki Kinoshita, Kazuhiro Hirohashi, Yasutoshi Tsuji, Eiichi Nagata, Shoji Kubo, Mikio Fujimoto*

Seocnd Division, Department of Surgery, Osaka City University Medical School
*Department of Surgery, Fujiidera Municipal Hospital

The effect of bile-duct pressure on biliary excretion of the antibiotic flomoxef sodium (FMOX) was studied experimentally in healthy male beagles. The free end of a tube inserted in the common bile duct was fixed at a height of -10 (A), 0 (B), 10 (C) or 20 (D) cm from the anterior duct wall. An intravenous injection of 50 mg/kg FMOX was given, and the drug concentration was assayed in the serum and bile during the next 5 hr. As the bile-duct pressure increased, total bile flow and total bile acid excretion decreased (A, 15.5 ml and 607 µmol; B, 8.8 and 351; C, 7.7 and 20l; D, 7.6 and 298). As the pressure increased, the biliary recovery and biliary Cmax decreased and the time of Cmax was delayed. (9.6%,5770 µg/ml, and 1∼1.5 hr for A; 5.4, 6037, and 1.5∼2 for B; 4.6, 5170, and 2∼3 for C; 3.1, 3257, and 2∼3 for D). There was no difference in the biological half-life, area under the curve, or total body clearance at different bile-duct pressures. However, the pharmacokinetic parameters of biliary excretion decreased and the lag time was prolonged with increased pressure. Apparently the bile-duct pressure affects the excretion of antibiotics into the bile.

Key words
bile-duct pressure, biliary excretion, pharmacokinetics, antibiotics

Reprint requests
Koji Nakata Second Department of Surgery, Osaka City Univesity Medical School
1-5-7 Asahi-machi, Abeno-ku, Osaka, 545 JAPAN

Accepted
October 11, 1989

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