Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC.

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed.

Impact of Laparotomy and Intraperitoneal Hyperthermic Instillation (LIHI) on the oxaliplatin pharmacokinetics after intravenous administration in Wistar rats.

PURPOSE: In peritoneal metastasis condition, the fact that most of the disease is limited to the peritoneal cavity laid the foundations for a surgical treatment, including intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of this study was to evaluate the impact of the surgical procedures implied in open HIPEC technique, referred to laparotomy procedures followed by an intraperitoneal hyperthermic instillation (LIHI) on oxaliplatin tissue distribution and elimination. To delimit the influence of this procedure alone, oxaliplatin was administered as an intravenous (iv) bolus in both groups. METHODS: An experimental model in Wistar rats was employed, and LIHI was evaluated as a dichotomous covariate by using a population pharmacokinetic (PK) approach. Rats were randomized in two groups receiving 1.5 mg iv oxaliplatin alone or 1.5 mg iv oxaliplatin under LIHI conditions, carrying out a hyperthermic 5% dextrose instillation. The oxaliplatin plasma concentrations were characterized by an open two-compartment PK model. RESULTS: Results concluded that surgical conditions affect the oxaliplatin elimination and distribution from blood to peripheral tissues, increasing the systemic drug exposure. Concretely, oxaliplatin peripheral volume of distribution, and clearance decreased by 48.6% and 55.3%, respectively, compared to the control group that resulted in a two-fold increase of the area under the concentration time curve. CONCLUSIONS: Comparison in clinical practice of oxaliplatin PK parameters obtained after iv administrations with those obtained after HIPEC interventions must be done carefully. This would limit the use of iv PK parameters to simulate new scenarios for oxaliplatin in HIPEC.

Outpatient treatment in uncomplicated acute diverticulitis: 5-year experience.

BACKGROUND/AIMS: Most cases of diverticular inflammation are mild and require only medical treatment with liquid diet and antibiotics. Until recently, this treatment required admission to hospitals, which consequently entailed costs. In most cases, treatment was conservative, and less than a quarter of patients admitted actually underwent surgery. In the last year, the outpatient treatment of these patients with uncomplicated diverticulitis has proven effective and safe. The aim of the present study was to describe our experience after 5 years of outpatient treatment with oral antibiotics. MATERIALS AND METHODS: We conducted a retrospective revision study between January 2010 and December 2014. We included all patients admitted to the Emergency Department of the University General Hospital of Elche with a diagnosis of uncomplicated acute diverticulitis based on medical history, physical examination and abdominopelvic computed tomography (CT) scanning. Outpatient treatment consisted of oral antibiotics for 10 days (metronidazole 500 mg/8 h and ciprofloxacin 500 mg/12 h), a liquid diet and oral analgesics (acetaminophen 1 g/6 h). RESULTS: During the period from January 2010 to December 2014, 224 patients were treated on an outpatient basis at a success rate of over 92%. Only 18 patients (8%) required admission after outpatient treatment. CONCLUSION: Outpatient treatment of uncomplicated acute diverticulitis was demonstrated to be safe and effective.