Satoru Kariya

Stereoselective high-performance liquid chromatographic determination of ketamine and its active metabolite, norketamine, in human plasma

A stereoselective high-performance liquid chromatographic method for the determination of the enantiomers of ketamine and its active metabolite, norketamine, in human plasma is described. The compounds were extracted from plasma by liquid-liquid extraction three times in a combination of cyclohexane with 2.5 M NaOH, 1 mM HCl and 1 M carbonate buffer. Stereoselective separation was achieved on a Chiralcel OD column with a mobile phase of n-hexane-2-propanol (98:2, v/v). The detection wavelength was 215 nm. The lower limits of the determination of the method were 5 ng/ml for ketamine and 10 ng/ml for norketamine. The intra- and inter-day coefficients of variation ranged from 2.9 to 9.8% and from 3.4 to 10.7% for all compounds, respectively. The method was sensitive and sufficiently reproducible for stereoselective monitoring of ketamine and norketamine in human plasma during pharmacokinetic studies after the administration of ketamine for analgesia.

Relationship between Kaposi's varicelliform eruption in Japanese patients with atopic dermatitis treated with tacrolimus ointment and genetic polymorphisms in the IL-18 gene promoter region

Kaposis varicelliform eruption is the most important problem in treating patients with atopic dermatitis (AD) with tacrolimus ointment. It has been considered that Kaposis varicelliform eruption occurs due to decreased levels of interleukin (IL)‐18. The aim of this study was to examine the relationship between Kaposis varicelliform eruption and genetic polymorphisms in the IL‐18 gene. IL‐18 gene promoter polymorphisms were analyzed in 21 AD patients treated with tacrolimus ointment and in 100 healthy volunteers. Six AD patients with Kaposis varicelliform eruption during the treatment with tacrolimus ointment showed significantly higher frequency in G‐to‐C mutations at the IL‐18 gene promoter region –137 compared with 15 AD patients without Kaposis varicelliform eruption. The 15 AD patients without Kaposis varicelliform eruption as well as 100 healthy volunteers did not have mutations of G‐to‐C at the IL‐18 gene promoter region –137. These results suggest that the onset of Kaposis varicelliform eruption following the treatment with tacrolimus ointment is associated with the mutation of G‐to‐C in the IL‐18 gene promoter region –137, and that caution is required when using tacrolimus ointment for treating AD patients with this mutation.