PHarmacokinetics of sulbactam and cefoperazone given in combination to patients on hemodialysis

• Published in: Journal of Japanese Society for Dialysis Therapy Vol. 22; no. 10; pp. 1133 - 1138
• Main Authors: Yamamoto, Noritoshi, Tanaka, Hideki, Takamitsu, Yoshihiro, Yura, Takafumi, Takahashi, Norihiro, Matsuo, Hirohide, Miki, Shigehiro, Yuasa, Shigekazu, Yoshida, Kanji, Uchida, Kouichi, Sumikura, Touru, Bandai, Hisashi, Kiyomoto, Hideyasu
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Society for Dialysis Therapy 1989
• Subjects: sulbactam/cefoperazone
• ISSN: 0911-5889; 1884-6211
• DOI: 10.4009/jsdt1985.22.1133

The purpose of this study was to examine the pharmacokinetic profiles of two antibiotics, sulbactam (0.5g) which is primarily eliminated renally, and cefoperazone (0.5g) which is primarily eliminated hepatically, coadministered intravenously to six normal subjects and seven hemodialysis patients both during and between hemodialysis treatments. All subjects had normal liver function. For sulbactam the elimination half life (T1/2) was 0.83±0.07h in normal subjects, but 7.3±4.8h in patients between hemodialysis treatments. The sulbactam T1/2 in patients changed significantly, however, approaching the level of normal subjects, during hemodialysis (0.92±0.21h). The hemodialysis clearance of sulbactam measured in four patients was 133.5±8.1ml/min. For cefoperazone T1/2 was 1.6±0.2h in normal subjects, 3.7±2.8h in patients between hemodialysis treatments, and 1.8±1.0h in those undergoing hemodialysis. The difference in T1/2 between and during hemodialysis sessions was not significant. The hemodialysis clearance of cefoperazone was 31.5±7.9ml/min, showing low hemodialysis extraction. Assuming that the combination of both drugs was given twice a day for 1 week to patients undergoing hemodialysis treatment 3 times a week, we calculated the changes in serum concentration of both drugs by using the pharmacokinetic data obtained. The maximal concentration of sulbactam during the week was about 130% of the peak concentration obtained following the first administration. The concentration of cefoperazone remained almost fixed. Based on these data a dosing regimen involving a 1:1 combination of sulbactam (0.5g) and cefoperazone (0.5g) every 12h is recommended for hemodialysis patients. If the patient's condition demands a higher serum concentration of antibiotics, an additional dose of cefoperazone alone may be administered.