Pharmacokinetics and tissue penetration of a single dose of ornidazole (1,000 milligrams intravenously) for antibiotic prophylaxis in colorectal surgery

Abstract

Levels in serum and tissue penetration of ornidazole were studied after a single intravenous injection of 1,000 mg given to 14 patients for prophylaxis of surgical infection. They were scheduled for elective colorectal surgery. Adequate levels in blood (2MIC for 90% of Bacteroides fragilis strains tested) were found in all patients throughout the procedure and up to hour 24. Mean-maximal (15 min) and last-determined (24 h) ornidazole levels in serum were 24 5.2 and 6.3 1.4 mg/liter, respectively. 13-Phase elimination half-life was 14.1 + 2.7 h, and clearance and apparent volume of distribution were 47 + 12 ml/min and 0.9 + 0.13 liters/kg, respectively. In all patients, adequate levels in tissue were found in the abdominal wall and the epiploic fat at time of incision and in the colonic wall at time of anastomosis. At time of closure, all but one patient had adequate levels in tissue in the abdominal wall and the epiploic fat. No anaerobic nor aerobic infection occurred in the study patients.The benefit of short-term antimicrobial courses for prevention of postoperative infection has been demonstrated for selected surgical procedures, among them colorectal surgery (4,11,23). Antimicrobial agents for prophylaxis should be selected on the basis of their spectrum of activity against pathogens most likely to contaminate the surgical wound (11). Since Bacteroides fragilis and other anaerobic bacteria are among the main pathogens encountered in infections after colorectal surgery, antibiotics with a spectrum of activity extended to these organisms are usually advocated (1). Antibiotic regimens which do not eliminate anaerobic fecal pathogens fail to control postoperative septic complications of colorectal operations (5, 13).Nitroimidazole derivatives such as metronidazole are commonly used in this situation (3,8,12,22 MATERIALS AND METHODSThis study received the approval of the ethical committee of our institution, and all patients gave their informed consent. Fourteen patients were scheduled for elective rectal or colonic surgery. They were 10 men and 4 women with a mean age of 66 5 years and a mean weight of 67 + 8 kg. None had a history of allergic reaction to ornidazole. All patients had normal renal and hepatic function. They had a 2-day mechanical bowel preparation consisting of low-residue diet, purgation, and bowel washouts in the evening. Patients did not present any clinical or laboratory signs of infection and were not receiving any antibiotic therapy before surgery. Before induction of anesthesia, patients were given a single dose of 1,000 mg of ornidazole intravenously (i.v.) administered over 30 min via an arm catheter, at a constant flow rate with an automatic pump. Blood samples were collected from a central venous line (right internal jugular vein) before ornidazole injection and 15 min (maximum concentration), 45 min, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24

Concentrations in plasma and tissue penetration of ceftriaxone and ornidazole during liver transplantation

“…The penetration rates found in the present study are similar to those described in other studies during classical gut surgery (12). However, our results might also take into account the fact that perioperative conditions during liver transplantation may modify blood and/or tissue drug concentrations.…”

“…These drugs were chosen because of their known pharmacokinetic properties and their spectra of activity (3,12,16). Plasma and epiploic fat drug concentrations were determined until the end of the surgical procedure.…”

Pharmacokinetics and tissue penetration of a single 1,000-milligram, intravenous dose of metronidazole for antibiotic prophylaxis of colorectal surgery

“…The penetration into fatty tissue relative to drug concentrations in serum was estimated to be from 10 to 13% in the study patients (Table 1). In another study performed under similar clinical conditions, ornidazole demonstrated a higher tissue penetration into fatty tissue (from 23 to 26%) and 84 to 100% of patients had ornidazole levels in tissue >MICgo for B. fragilis (15). What constitutes optimal tissue levels of antibiotics is poorly understood (2).…”

“…The metronidazole levels in serum and pharmacokinetic parameters of the study patients were as follows: maximum level (at 15 (1,10,20), and the main points are as follows. (i) The antimicrobial agent must be present in the involved tissues before surgery allows bacterial contamination.…”

Stereoselective Glucuronidation of Ornidazole in Humans: Predominant Contribution of UDP-Glucuronosyltransferases 1A9 and 2B7

“…Clinical studies have shown that the maximal plasma concentration of the therapeutic dose (121.5 g/d) of ornidazole was around 100 mM (Martin et al, 1990;Li et al, 2002;Wang et al, 2008;Wei et al, 2010). Therefore, the UGT isoform screening experiment was conducted at 100 mM and higher substrate concentrations (1 and 50 mM), in case of missing isoforms with low affinity.…”