Assessing carbamazepine and oxcarbazepine-associated Stevens-Johnson syndrome/toxic epidermal necrolysis: Data mining the public version of the FDA adverse event reporting system.

AIMS: Stevens-Johnson syndrome and toxic epidermal necrolysis are viewed as the most severe drug-induced types of cutaneous adverse reactions, with high rates of morbidity and mortality. We aimed to examine carbamazepine- and oxcarbazepine-associated Stevens-Johnson syndrome or toxic epidermal necrolysis, by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Reports in FAERs were analysed, from the first quarter of 2004 to the last quarter of 2019. Pharmacovigilance tools were employed for the quantitative detection of signals, where a signal represents a drug-associated adverse event, including the reporting odds ratio, proportional reporting ratio, an information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. RESULTS: The total number of reports identified as Stevens-Johnson syndrome or toxic epidermal necrolysis associated with carbamazepine or oxcarbazepine included in this study was 1231. FAERS reports associated with carbamazepine were 1048, including Stevens-Johnson syndrome (n = 668) and toxic epidermal necrolysis(n = 380). FAERS reports associated with oxcarbazepine were 183, including 142 Stevens-Johnson syndrome and 41 toxic epidermal necrolysis reports. The risk for Stevens-Johnson syndrome is higher than for toxic epidermal necrolysis and carbamazepine is associated with a higher risk than oxcarbazepine. CONCLUSIONS: The results of our study are consistent with clinical observations, suggesting the necessity for further clinical research on Stevens-Johnson syndrome and toxic epidermal necrolysis associated with carbamazepine or oxcarbazepine.

Investigation of inclusion complex of honokiol with sulfobutyl ether-ß-cyclodextrin.

This study aimed to prepare and characterize an inclusion complex of honokiol (HNK) with sulfobutyl ether-ß-cyclodextrin (SB-ß-CD). The inclusion complex (HNK/CD COMP) was prepared utilizing a freeze-drying method. Phase-solubility curves were employed to obtain stability constants and thermodynamic parameters. The phase-solubility diagram showed a typical A(L)-type, indicating that the 1:1 (HNK:SB-ß-CD) inclusion complex was formed. The solid inclusion complex was then characterized by differential scanning calorimetry and Fourier transform infrared spectroscopy. Results showed that HNK/CD COMP exhibited a higher drug release rate than free HNK in vitro. A comparative study of the pharmacokinetics between HNK/CD COMP and free HNK was also performed in rats. In vivo results indicated that AUC0-t and Cmax of HNK/CD COMP increased by approximately 158% and 123% compared with those of the free HNK, respectively. These results suggest that SB-ß-CD will be potentially useful in the delivery of poorly soluble drugs, such as HNK.