Shinnosuke Uegami

Pharmacokinetics and pharmacodynamic target attainment of intravenous pazufloxacin in the bile of patients undergoing biliary pancreatic surgery

Abstract The study aimed to characterize the pharmacokinetics and pharmacodynamics of pazufloxacin (PZFX) in bile and to identify optimal dosing regimens. Pazufloxacin 500 mg was administered via a 0·5-hour intravenous infusion to 10 patients with endoscopic nasal bile drainage before or after biliary pancreatic surgery. Both blood and bile samples were collected pre-dose and at the end of infusion (0·5 hours) and for up to 5 hours thereafter. Concentrations of PZFX were determined using high-performance liquid chromatography. Noncompartmental and compartmental pharmacokinetic parameters were estimated, and Monte Carlo simulation was conducted to evaluate the pharmacodynamic exposure of PZFX in bile. The bile/plasma ratios were 3·58±1·15 in the area under the drug concentration–time curve (AUC) and 2·13±0·74 in the maximum drug concentration (Cmax). The delay in the time to Cmax, from plasma to bile, was 0·75±0·18 hours The probability of attaining pharmacodynamic targets (both AUC/MIC = 100 and Cmax/MIC = 8) in bile against a minimum inhibitory concentration (MIC) of 2 mg/l was >90% when PZFX was administered by a 0·5-hour infusion with 500 mg every 8 hours or 1000 mg every 12 hours These regimens provided an adequate antibacterial effect against the most common pathogens of biliary tract infections, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae with their MICs<2 mg/l.

Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and peritoneum of surgery patients, and dosing considerations based on site-specific pharmacodynamic target attainment

Piperacillin-tazobactam (PIP-TAZ) is commonly used to treat intraabdominal infections; however, its penetration into abdominal sites is unclear. A pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug concentrations was conducted to simulate dosing regimens needed to attain the pharmacodynamic target in abdominal sites. PIP-TAZ (4 g-0.5 g) was intravenously administered to 10 patients before abdominal surgery for inflammatory bowel disease. Blood, peritoneal fluid, and peritoneum samples were obtained at the end of infusion (0.5 h) and up to 4 h thereafter. PIP and TAZ concentrations were measured, both noncompartmental and compartmental pharmacokinetic parameters were estimated, and a simulation was conducted to evaluate site-specific pharmacodynamic target attainment. The mean peritoneal fluid:plasma ratios in the area under the drug concentration-time curve (AUC) were 0.75 for PIP and 0.79 for TAZ, and the mean peritoneal fluid:plasma ratios in the AUC were 0.49 for PIP and 0.53 for TAZ. The mean PIP:TAZ ratio was 8.1 at both peritoneal sites. The regimens that achieved a bactericidal effect with PIP (time above minimum inhibitory concentration [MIC] >50%) at both peritoneal sites were PIP-TAZ 4.5 g twice daily for an MIC of 8 mg/L, as well as 4.5 g three times daily, and 3.375 g four times daily for an MIC of 16 mg/L. These findings clarify the peritoneal pharmacokinetics of PIP-TAZ, and help consider the dosing regimens for intraabdominal infections based on site-specific pharmacodynamic target attainment.

Inguinoscrotal hernia containing the urinary bladder successfully repaired using laparoscopic transabdominal preperitoneal repair technique: A case report: Inguinal bladder hernia

We report herein a patient with an inguinoscrotal hernia containing the urinary bladder. The hernia was safely repaired using the laparoscopic transabdominal preperitoneal repair technique. A 76‐year‐old man was admitted to our hospital with abdominal pain, vomiting, and diarrhea. His scrotum was swollen to fist size. Abdominal CT showed herniation of the sigmoid colon and the bladder into the right inguinal region, and his abdominal pain was attributed to incarceration of the sigmoid colon; this was manually reduced. About 1 month later, we performed transabdominal preperitoneal repair. After the direct hernial orifice was identified, the bladder was noted to be sliding from the medial side of the hernia; this was reduced. Peeling on the medial side was carried out to the middle of the abdominal wall, and the myopectineal orifice was covered with mesh. The patient was discharged on postoperative day 1.

Hand-assisted laparoscopic restorative proctocolectomy for ulcerative colitis.

AIM To evaluate the utility of hand-assisted laparoscopic restorative proctocolectomy (HALS-RP) compared with the conventional open procedure (OPEN-RP). METHODS Fifty-one patients who underwent restorative total proctocolectomy with rectal mucosectomy and ileal pouch anal anastomosis between January 2008 and July 2015 were retrospectively analyzed. Twenty-three patients in the HALS-RP group and twenty-four patients in the OPEN-RP group were compared. Four patients who had purely laparoscopic surgery were excluded. Restorative total proctocolectomy was performed with mucosectomy and a hand-sewn ileal-pouch-anal anastomosis. Preoperative comorbidities, intraoperative factors such as blood loss and operative time, postoperative complications, and postoperative course were compared between two groups. RESULTS Patients in both groups were matched with regards to patient age, gender, and American Society of Anesthesiologists score. There were no significant differences in extent of colitis, indications for surgery, preoperative comorbidities, and preoperative medications in the two groups. The median operative time for the HALS-RP group was 369 (320-420) min, slightly longer than the OPEN-RP group at 355 (318-421) min; this was not statistically significant. Blood loss was significantly less in HALS-RP [300 (230-402) mL] compared to OPEN-RP [512 (401-1162) mL, P = 0.003]. Anastomotic leakage was noted in 3 patients in the HALS-RP group and 2 patients in the OPEN-RP group (13% vs 8.3%, NS). The rates of other postoperative complications and the length of hospital stay were not different between the two groups. CONCLUSION HALS-RP can be performed with less blood loss and smaller skin incisions. This procedure is a feasible technique for total proctocolectomy for ulcerative colitis.

Two Cases of Severe Ulcerative Colitis with Colonic Dilatation Resolved with Tacrolimus Therapy

We report 2 cases of ulcerative colitis (UC) with intestinal tract dilatation treated with tacrolimus. They were 53- and 64-year-old males, who had been admitted to local hospitals for increasing severity of their UC symptoms. Treatment for severe UC was immediately started, but both cases were refractory to corticosteroid therapy; they were then transferred to our hospital. When they were referred to our hospital, they had frequent bloody diarrhea, fever, severe abdominal pain, and even dilatation of the transverse colon on abdominal X-ray test. They were treated with oral tacrolimus medication, and their symptoms improved immediately. Dilatation of the transverse colon was improved on plain X-ray at 2 weeks after starting therapy, and emergency colectomy could be avoided. These 2 cases may suggest that tacrolimus is effective for UC with colonic dilatation as a rescue therapy.