Background Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic. Case presentation A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of 100 tablets of loxoprofen (6000 mg) as a suicide attempt was emergently admitted to Kyoto Medical Center. On arrival, the patient was suffering disorders of consciousness. His plasma concentrations of loxoprofen and its reduced trans-alcohol metabolite were 52 and 24 μg/mL, 3.7 and 2.3 μg/mL, 0.81 and 0.54 μg/mL, and 0.015 and 0.011 μg/mL, respectively, at 4, 26, 50, and 121 h after the oral overdose. The observed apparent terminal elimination half-life of loxoprofen during days 1 and 2 of hospitalization was in the range 6–12 h, which is several times longer than the reported normal value. This finding implied nonlinearity of loxoprofen pharmacokinetics over the current 100-fold dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic (PBPK) model founded on data from a normal dose of 60 mg. The reasons for the delayed eliminations from plasma of loxoprofen and its trans-alcohol metabolite in this case are uncertain, but slight renal impairment (low eGFR values) developed on the second and third hospital days and could be a causal factor. Conclusions Because the patient’s level of consciousness had gradually improved, he was discharged on the fourth day of hospitalization. The virtual plasma exposures of loxoprofen and its reduced trans-alcohol metabolite estimated using the current simplified PBPK model were lower than the measured values in the overdose case. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide in cases of loxoprofen overdose.

Patient:A 32-year-old man with severe obesity and a BMI of 51.7 was hospitalized because of pneumonia. He underwent respiratory management with a mechanical ventilator; however, because the respiratory management was difficult (P/F ratio was around 50), he was transferred to the ICU. Transpulmonary pressure was monitored, and in order to address the decreased thoracic compliance and pressure on the diaphragm due to severe obesity, we conducted respiratory management with high PEEP, which resulted in an improvement in the respiratory condition. Furthermore, when we conducted continuous negative abdominal pressure management to improve the pressure on the diaphragm, the end-expiratory transpulmonary pressure was elevated under the same respiratory condition. Discussion: Avoiding lung injury related to the use of a mechanical ventilator is important during the management of respiratory failure, and lung-protective ventilation and the open lung approach are the primary strategies adopted for this purpose. Because of the high abdominal pressure in patients with severe obesity, alveolar collapse is enhanced by the decrease in transpulmonary pressure due to the pressure on the diaphragm. In the present patient, abdominal pressure was decreased because of continuous negative abdominal pressure management, and an elevation of end-expiratory transpulmonary pressure was observed under the same respiratory condition. We believe that the obtained change can improve atelectasis, thereby benefiting the open lung.

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