Oseltamivir Is Adequately Absorbed Following Nasogastric Administration to Adult Patients with Severe H5N1 Influenza

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy

Single-phase multilevel inverter based on switched-capacitor structure

This study proposes a new topology for multilevel inverters based on switched-capacitor structure. The proposed topology uses capacitor charged/discharged characteristic to boost the output voltage without employing magnetic elements. The proposed circuit configuration has fewer components, including switches, voltage sources, and capacitors comparing with the conventional similar topologies. A phase disposition pulse-width modulation method is used to enhance the output waveform quality of the proposed inverter. Nine-level and 17-level configurations are simulated. To verify the operating principle, the experimental results for a nine-level inverter topology are presented

Patients' clinical, pharmacokinetic and virological features.

*<p>Cockroft Gault formula.</p>¶<p>Arterial blood gas prior to ventilation, mmHg: PO₂, PCO₂, mmol/L:HCO₃⁻.</p>#<p>OP = oseltamivir phosphate, OC = oseltamivir carboxylate.</p

Viral clearance in patients A.

<p>Day 0 is the day of illness onset.</p

Viral clearance in patient C.

<p>Day 0 is the day of illness onset.</p

Oseltamivir carboxylate (OC) concentrations taken from the arterial (a) limb of the haemofilter (from the patient) and the venous (v) haemofilter (to the patient).

<p>For clarity, the OC concentrations from the exit limb (e) to the effluent bags are shown for Patient C only. Sampling for Patient A was off the haemofilter.</p