IdB 1016 is a complex of silybin (the main active component of silymarin) and phosphatidylcholine, which in animal models shows greater oral bioavailability and therefore greater pharmacological activity compared with pure silybin and silymarin. In order to assess its pharmacokinetic profile in man, plasma silybin levels were determined after administration of single oral doses of IdB 1016 and silymarin (equivalent to 360 mg silybin) to 9 healthy volunteers. Although absorption was rapid with both preparations, the bioavailability of IdB 1016 was much greater than that of silymarin, as indicated by higher plasma silybin levels at all sampling times after intake of the complex. Regardless of the preparation used, the terminal half-life was relatively short (generally less than 4 h). In a subsequent study, 9 healthy volunteers received IdB 1016 (120 mg b.i.d., expressed as silybin equivalents) for 8 consecutive days. The plasma silybin level profiles and kinetic parameters on day 1 were similar to those determined on day 8. Most of the silybin present in the systemic circulation was in conjugated form. Less than 3% of the administered dose was accounted for by urinary recovery of free plus conjugated silybin, a significant proportion of the dose probably being excreted in the bile. It is concluded that complexation with phosphatidylcholine in IdB 1016 greatly increases the oral bioavailability of silybin, probably by facilitating its passage across the gastrointestinal mucosa.

The current mortality of IE remains high, and is mainly due to its complications, such as CHF and stroke.

1. The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme‐inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2. Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven‐fold (P less than 0.01) in patients taking enzyme‐inducing anticonvulsants and increased by about 50% (P less than 0.05) in patients taking sodium valproate. 3. Nimodipine half‐lives were shorter in enzyme‐induced patients than in controls (3.9 +/‐ 2.0 h vs 9.1 +/‐ 3.4 h, means +/‐ s.d., P less than 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate‐treated patients, half‐lives (8.2 +/‐ 1.8 h) were similar to those found in controls.

Candida species are an uncommon cause of infective endocarditis (IE). Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy of Candida IE are poorly defined. We conducted a prospective, observational study at 18 medical centers in Italy, including all consecutive patients with a definite diagnosis of IE admitted from January 2004 through December 2007.A Candida species was the causative organism in 8 cases of prosthetic valve endocarditis (PVE), 5 cases of native valve endocarditis (NVE), 1 case of pacemaker endocarditis, and 1 case of left ventricular patch infection. Candida species accounted for 1.8% of total cases, and for 3.4% of PVE cases. Most patients (86.6%) had a health care-associated infection. PVE associated with a health care contact occurred after a median of 225 days from valve implantation. Ten patients (66.6%) were treated with caspofungin alone or in combination with other antifungal drugs. The overall mortality rate was 46.6%. Mortality was higher in patients with PVE (5 of 8 cases, 62.5%) than in patients with NVE (2 of 5 patients, 40%). A better outcome was observed in patients treated with a combined medical and surgical therapy.Candida IE should be classified as an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial related morbidity and mortality. Candida PVE usually is a late-onset disease, which becomes clinically evident even several months after an initial episode of transient candidemia.

Following the initial resuscitation of burn patients, the pain experienced may be divided into a 'background' pain and a 'breakthrough' pain associated with painful procedures. While background pain may be treated with intravenous opioids via continuous infusion or patient-controlled analgesia (PCA) and/or less potent oral opioids, breakthrough pain may be treated with a variety of interventions. The aim is to reduce patient anxiety, improve analgesia and ensure immobilization when required. Untreated pain and improper sedation may result in psychological distress such as post-traumatic stress disorder, major depression or delirium. This review summarizes recent developments and current techniques in sedation and analgesia in non-intubated adult burn patients during painful procedures performed outside the operating room (e.g. staple removal, wound-dressing, bathing). Current techniques of sedation and analgesia include different approaches, from a slight increase in background pain therapy (e.g. morphine PCA) to PCA with rapid-onset opioids, to multimodal drug combinations, nitrous oxide, regional blocks, or non-pharmacological approaches such as hypnosis and virtual reality. The most reliable way to administer drugs is intravenously. Fast-acting opioids can be combined with ketamine, propofol or benzodiazepines. Adjuvant drugs such as clonidine or NSAIDs and paracetamol (acetaminophen) have also been used. Patients receiving ketamine will usually maintain spontaneous breathing. This is an important feature in patients who are continuously turned during wound dressing procedures and where analgo-sedation is often performed by practitioners who are not specialists in anaesthesiology. Drugs are given in small boluses or by patient-controlled sedation, which is titrated to effect, according to sedation and pain scales. Patient-controlled infusion with propofol has also been used. However, we must bear in mind that burn patients often show an altered pharmacokinetic and pharmacodynamic response to drugs as a result of altered haemodynamics, protein binding and/or increased extracellular fluid volume, and possible changes in glomerular filtration. Because sedation and analgesia can range from minimal sedation (anxiolysis) to general anaesthesia, sedative and analgesic agents should always be administered by designated trained practitioners and not by the person performing the procedure. At least one individual who is capable of establishing a patent airway and positive pressure ventilation, as well as someone who can call for additional assistance, should always be present whenever analgo-sedation is administered. Oxygen should be routinely delivered during sedation. Blood pressure and continuous ECG monitoring should be carried out whenever possible, even if a patient is undergoing bathing or other procedures that may limit monitoring of vital pulse-oximetry parameters.