In our previous drug poisoning cohort study of patients admitted to a hospital emergency room between January 2018 and March 2021, flunitrazepam, diphenhydramine, etizolam, quetiapine, lorazepam, and triazolam were ranked the top six drugs among substances causing acute poisoning resulting in admissions of patients after suicide attempts. Simplified physiologically based pharmacokinetic (PBPK) models were established for these six drugs using reported pharmacokinetic data after normal doses. The elimination rates of the six drugs from human plasma were relatively slow after oral administration. High virtual exposures of these drugs were estimated using the current PBPK models, and some linearity of pharmacokinetics over a wide dosage range was evident. Univariate analysis showed that total clearance values (the sum up of hepatic and renal clearances) for use in our PBPK models were significantly correlated with one of the drugs' physicochemical parameters, namely octanol–water partition coefficients. This simple method for estimating drug clearances may be useful for generating approximate elimination rates for similar types of drugs. The present pharmacokinetic predictions could serve as a useful guide when setting the required duration of treatment in overdose cases resulting in acute poisoning in emergency rooms.

We performed continuous hemodiafiltration (CHDF) and hemodialysis (HD) in two patients suspected of severe acute caffeine intoxication and could save their lives. Caffeine clearance (CL) and elimination half-life (t_1/2) were calculated and assessed for performing effective blood purification.

Blood caffeine concentration was quantified using gas chromatography/mass spectrometry, and CL and t_1/2 were calculated. The blood caffeine concentrations in Case 1 and Case 2 on arrival were 86 μg/mL and 135 μg/mL, respectively, reaching the lethal level. Caffeine CL values for CHDF and HD were 3-29 mL/min and 132-149 mL/min, respectively, and t_1/2 values were 12 h and 3.5 h, respectively.

For cases suspected of severe acute caffeine intoxication, it is desirable to select (1) HD, (2) direct hemoperfusion (DHP), or (3) their combination. It was considered desirable to perform multiple HDs for cases wherein a high blood caffeine concentration was expected. For cases wherein performing HD or DHP is difficult, it is desirable to first choose CHDF and then switch to HD or DHP.

Tramadol is a weak opioid analgesia commonly prescribed for elderly patients. We report here a case of type 2 respiratory failure possibly caused by tramadol. An 87-year-old man with impaired consciousness was brought to our emergency room. Blood gas analysis showed respiratory acidosis, and carbon dioxide narcosis was suspected as the cause of his impaired consciousness. He also had renal impairment with a creatinine clearance of 16 mL/min. The cause of respiratory depression was suspected to be tramadol, which had been increased to 200 mg/day for postherpetic neuralgia at the pain clinic 3 days earlier. We measured the blood concentration of tramadol and found it to be as high as 370 ng/mL. Metabolism of tramadol and its metabolites is known to be delayed in renal impairment and in elderly cases. Given that respiratory depression can occur even at the usual dose, caution should be exercised when increasing the dose of tramadol in elderly patients.