Purpose: Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China.Methods: Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). At the same time, we also collated drug combinations that may affect CYP (Cytochrome P) enzyme metabolism, which may cause DILI.Results: A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while the hepatic injury types of children were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the RUCAM assessment, the drugs that were most considered to cause or be associated with hepatic injury in newborns were medium and long chain fat emulsions (17%), sodium glycerophosphate (12%), and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%), and meropenem (8%) were the primary culprits of DILI in children. Drug combinations frequently seen in neonates that may affect CYP enzyme metabolism are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%), and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%), and diazepam + omeprazole (15.3%).Conclusions: In this study, medium and long chain fat emulsions and sodium glycerophosphate have been strongly associated with DILI in newborns, while omeprazole and methylprednisolone sodium succinate play an important role in the DILI of children. Also, attention should be paid to the effect on CYP enzymes when using multiple drugs at the same time. In future DILI cases, it is advisable to use the latest RUCAM for prospective study design so that complete case data and high RUCAM scores can be collected.

Abiraterone acetate tablets (I)(N-AbA) is a novel tablet co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). This study aimed to compare the pharmacokinetics, bioequivalence, safety, and food effects of N-AbA with the reference ZYTIGA ® (R-AbA) in healthy Chinese male subjects. Patients and Methods: This study was conducted in three parts. Part I was an open, doseescalation trial conducted in 16 Chinese healthy males; Part II was a randomized, open-label, 2 × 4 crossover, single-dose bioequivalence trial conducted in 36 subjects; Part III was a randomized, 3 × 3 crossover trial conducted on 24 volunteers to investigate the effect of food on the pharmacokinetics of N-AbA. Results:The exposure (AUC 0-∞ ) and maximum concentration (C max ) of abiraterone and excipient SNAC were linear in the range of 75-450 mg dose. The bioavailability of N-AbA 300 mg was equivalent to that of R-AbA 1000 mg. The drug exposure of prednisone and prednisolone was not affected by SNAC co-administration. The C max of orally administered abiraterone as R-AbA in a modified fed state was 5.9 times and AUC 0-∞ was 4.3 times, respectively, higher than those in of orally administered abiraterone as N-AbA in a high-fat diet. The C max and AUC 0-∞ of orally administered abiraterone as N-AbA on a high-fat diet were 2.2 times and 2 times, respectively, higher than those on a fasting state. All adverse events reported in the three parts of the study were grade 1 or 2, and no serious adverse events were reported. Conclusion: These three Phase I trials showed that N-AbA and excipient SNAC had excellent linear pharmacokinetic characteristics. A single dose of N-AbA 300 mg was bioequivalent to R-AbA 1000 mg in healthy subjects under fasting conditions. Meanwhile, SNAC had no effect on the pharmacokinetics of prednisone and prednisolone. The effect of food on N-AbA was significantly lower than that on R-AbA.

Background: Drug-induced acute kidney injury (DIKI) is a common adverse drug reaction event but is less known in pediatric patients. The study explored the DIKI in Chinese pediatric patients using the Pediatric Intensive Care database (PIC).Method: We screened pediatric patients with acute kidney injury (AKI) using the KDIGO criteria from the PIC and then assessed the relationship between their drugs and DIKI using the Naranjo scale. For the fifteen frequently used DIKI-suspected drugs, we divided patients into drug-exposed and non-exposed groups, using the outcome of whether DIKI was presented or not. Propensity score matching (PSM) was used to control for the effects of four confounders, age, gender, length of hospital stay, and major diagnosis. Unconditional logistic regression was used to identify statistically significant differences between the two groups.Results: A total of 238 drugs were used 1,863 times by the 81 patients with DIKI during their hospital stay. After screening the Naranjo scale to identify the top 15 suspected DIKI drugs with a high frequency of use, we found that furosemide injection (p = 0.001), midazolam injection (p = 0.001), 20% albumin prepared from human plasma injection (p = 0.004), fentanyl citrate injection (p = 0.001), compound glycyrrhizin injection (p = 0.026), vancomycin hydrochloride for intravenous (p = 0.010), and milrinone lactate injection (p = 0.009) were associated with DIKI.Conclusion: In critically ill pediatric patients, DIKI is more likely to occur after using furosemide injection, midazolam injection, 20% albumin prepared from human plasma injection, fentanyl citrate injection, compound glycyrrhizin injection, vancomycin hydrochloride for intravenous, milrinone lactate injection.