Pharmacokinetic and pharmacodynamic properties of biapenem, a carbapenem antibiotic, in rat experimental model of severe acute pancreatitis.
OBJECTIVE
It is known that prophylaxis with imipenem reduces the risk of infection accompanying severe acute pancreatitis. In this study,we modified a rat experimental model of severe acute pancreatitis for antibiotic evaluation, and the effect of biapenem was compared with that of imipenem to determine the usefulness of biapenem.


METHODS
Severe acute pancreatitis was induced by 5% sodium taurocholate. Antibiotics were subcutaneously administered at 3 and 6 hours and evaluated at 12 hours after the pancreatitis induction. For pharmacokinetic evaluation, antibiotics were subcutaneously administered at 3 hours after the pancreatitis induction.


RESULTS
From 3 hours after the induction, bacteria were detected from the pancreas. The total bacterial count increased in a time-dependent manner for 12 hours. Biapenem administration reduced the total bacterial count in the pancreas, as observed in imipenem administration. The plasma concentration of biapenem was almost equivalent to that of imipenem; however, the pancreatic penetration of biapenem was approximately twice that of imipenem in this model.


CONCLUSIONS
Biapenem was suggested to be effective in prophylactic treatment of infectious complications as much as imipenem because of its superior penetration to the pancreas in severe acute pancreatitis.
Muto
Yuko
Y
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. yuko_muto@meiji.co.jp
Mikami
Yukio
Y
Sakakibara
Shiro
S
Shimizu
Atsuyuki
A
Niida
Masashi
M
Kataoka
Hiroshi
H
Ito
Fumi
F
Suzuki
Katsuyoshi
K
Kijima
Koji
K
Maebashi
Kazunori
K
Takata
Toshihiko
T
Hikida
Muneo
M
Takeda
Kazunori
K
Unno
Michiaki
M
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001201:Ascites / Q000382:microbiology; D001424:Bacterial Infections / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007422:Intestines / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D013656:Taurocholic Acid; D015378:Imipenem; C065257:biapenem