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33. Effects of CYP2D6and CYP3A5Genotypes on the Plasma Concentrations of Risperidone and 9-Hydroxyrisperidone in Korean Schizophrenic Patients

Author

Kang, Rhee-Hun, Jung, Sun-Min, Kim, Kyoung-Ah, Lee, Duk-Ki, Cho, Hyun-Kee, Jung, Bong-Joo, Kim, Young-Ku, Kim, Seung-Hyun, Han, Changsu, Lee, Min-Soo, and Park, Ji-Young

Abstract

This study was conducted to evaluate the effects of the CYP2D6and CYP3A5genotypes on the steady-state plasma levels of risperidone (RIS), 9-hydroxyrisperidone (9-OH-RIS), and the active moiety (RIS plus 9-OH-RIS) in Korean schizophrenic patients. Sixty-four Korean schizophrenic patients were enrolled. CYP2D6and CYP3A5genotypes were determined, and the plasma levels of RIS and 9-OH-RIS were measured using high-performance liquid chromatography. The dose-normalized plasma concentrations of RIS, 9-OH-RIS, and the active moiety were compared according to the CYP2D6and CYP3A5genotypes. Among the patients, 57 were CYP2D6extensive metabolizers (EMs; CYP2D61/1, 1/10, and 10/10) and 7 were CYP2D6poor metabolizers (PMs; CYP2D61/5and 10/5). For the CYP3A5genotype, 30 patients were CYP3A51expressors (1/1n = 1 and 1/3n = 29) and 34 patients were CYP3A5nonexpressors (3/3). The plasma levels of RIS (2.03 ng/mL per milligram for EMs vs 5.57 ng/mL per milligram for PMs, P< 0.001) and 9-OH-RIS (5.06 ng/mL per milligram for EMs vs 0.22 ng/mL per milligram for PMs, P< 0.001) were significantly different among CYP2D6genotype groups, but the CYP2D6EMs (7.09 ng/mL per milligram) and PMs (5.79 ng/mL per milligram) did not show no difference in the levels of the active moiety (P= 0.470). CYP3A5nonexpressors exhibited higher plasma concentrations of both RIS and 9-OH-RIS than its expressors. In the case of 9-OH-RIS, CYP3A5nonexpressors exhibited significantly higher concentrations than CYP3A5expressors (5.42 vs 3.51 ng/mL per milligram, P= 0.022). In addition, concentrations of the active moiety were also significantly different between the CYP3A5nonexpressors (8.39 ng/mL per milligram) and expressors (5.30 ng/mL per milligram, P= 0.005). In conclusion, both CYP2D6and CYP3A5genotypes affected plasma levels of RIS and 9-OH-RIS, whereas the active moiety levels were influenced only by the CYP3A5genotype but not by the CYP2D6genotype.

Published
2009
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34. Salivary levels of IL-1beta, IL-6, IL-8, and TNF-alpha in patients with burning mouth syndrome.

Author

Suh KI, Kim YK, and Kho HS

Subjects
Aged, Blood, Case-Control Studies, Female, Gingival Hemorrhage classification, Gingivitis classification, Humans, Middle Aged, Periodontal Index, Saliva metabolism, Salivary Proteins and Peptides analysis, Secretory Rate, Transferrin analysis, Burning Mouth Syndrome metabolism, Interleukin-1beta analysis, Interleukin-6 analysis, Interleukin-8 analysis, Saliva chemistry, Tumor Necrosis Factor-alpha analysis
Abstract

Objective: To compare salivary IL-1beta, IL-6, IL-8, and TNF-alpha levels between patients with burning mouth syndrome (BMS) and controls., Design: Forty female patients with BMS (mean age: 61.6+/-10.1 years) and 20 female control subjects (mean age: 65.1+/-9.0 years) were included in the study. Unstimulated (UWS) and stimulated whole saliva samples (SWS) were collected and their flow rates were determined. Salivary IL-1beta, IL-6, IL-8, and TNF-alpha levels and total protein concentration were also determined. Salivary transferrin level was determined to investigate the level of blood contamination in saliva samples. Gingival index of the subjects was also examined. Student's t-test, Pearson's correlation analysis, and analysis of covariance were used., Results: No significant differences were found in the salivary levels of IL-1beta, IL-6, IL-8, and TNF-alpha in BMS patients compared with controls. Salivary flow rates and their total protein concentrations did not differ significantly between the groups. The levels of salivary cytokines and total protein concentration correlated significantly with the level of blood contamination in both UWS and SWS., Conclusion: There were no differences in the salivary levels of IL-1beta, IL-6, IL-8, and TNF-alpha in BMS patients compared with controls. Cytokine levels in whole saliva were affected mainly by the amount of blood contamination.

Published
2009
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