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<i>In vitro</i> inhibitory effects of Wen‐pi‐tang‐Hab‐Wu‐ling‐san on human cytochrome P450 isoforms
Lee, H. W.,Kim, D. W.,Phapale, P. B.,Lim, M. ‐,S.,Park, J.,Seo, J. J.,Park, K. M.,Park, Y. ‐,K.,Yoon, Y. ‐,R. Blackwell Publishing Ltd 2011 Journal of clinical pharmacy and therapeutics Vol.36 No.4
<P><B>Summary</B></P><P><B>What is known and Objective: </B> Although Wen‐pi‐tang‐Hab‐Wu‐ling‐san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW–drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.</P><P><B>Methods: </B> The abilities of various WHW extracts to inhibit phenacetin O‐de‐ethylation (CYP1A2), tolbutamide 4‐methylhydroxylation (CYP2C9), omeprazole 4′‐hydroxylation (CYP2C19), dextromethorphan O‐demethylation (CYP2D6), chlorzoxazone 6‐hydroxylation (CYP2E1) and midazolam 1‐hydroxylation (CYP3A4) were assessed using human liver microsomes.</P><P><B>Results and Discussion: </B> WHW extract at concentrations up to 100 μ<SMALL>m</SMALL> showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC<SUB>50</SUB> values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 μg/mL, respectively.</P><P><B>What is new and Conclusion: </B> Our <I>in vitro</I> findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug–herb interactions when co‐administered with other medicines. However, <I>in vivo</I> human studies are needed to confirm these results.</P>
Revival of TE2A; a better chelate for Cu(II) ions than TETA?
Pandya, Darpan N.,Kim, Jung Young,Park, Jeong Chan,Lee, Hochun,Phapale, Prasad B.,Kwak, Wonjung,Choi, Tae Hyun,Cheon, Gi Jeong,Yoon, Young-Ran,Yoo, Jeongsoo Royal Society of Chemistry 2010 Chemical communications Vol.46 No.20
<P>A highly effective synthetic route for TE2A was developed and the <SUP>64</SUP>Cu-labeled TE2A complexes showed higher kinetic inertness and faster clearance than most commonly used TETA analogs.</P> <P>Graphic Abstract</P><P>A facile synthetic route for TE2A was developed and TE2A was found to make a more kinetically stable Cu(II) complex than TETA. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b925703a'> </P>
Pharmacokinetics of prothionamide in patients with multidrug-resistant tuberculosis.
Lee, H W,Kim, D W,Park, J H,Kim, S-D,Lim, M-S,Phapale, P B,Kim, E-H,Park, S K,Yoon, Y-R The Union 2009 The international journal of tuberculosis and lung Vol.13 No.9
<P>SETTING: National Masan Tuberculosis Hospital, Masan, South Korea. OBJECTIVE: To evaluate the pharmacokinetics of prothionamide (PTH) in South Korean patients with multidrug-resistant tuberculosis (MDR-TB) and to investigate whether differences in body mass index (BMI) could explain observed differences in PTH disposition. DESIGN: Seventeen patients participated in the study; all had MDR-TB and had received combination anti-tuberculosis treatment, including PTH, cycloserine, ofloxacin, para-aminosalicylic acid and streptomycin or kanamycin, for at least 2 weeks. The patients were divided into two groups based on BMI: Group A (18.5 < or = BMI<23), and Group B (BMI<18.5). Serum samples were collected over 24 h, and the plasma PTH concentration was determined by a validated high-performance liquid chromatography assay. RESULTS: After steady-state administration of PTH, the mean area under the plasma concentration-time curve from time 0 to 12 h (AUC(0-12h)) was 11.0 +/- 3.7 microg h/ml. The mean T(max) and t(1/2) were respectively 3.6 h and 2.7 h. No significant difference in PTH disposition was observed between groups A and B, except for ke and t(1/2). CONCLUSION: In the pharmacokinetic parameter estimates for PTH in MDR-TB patients during routine treatment, the pharmacokinetics of PTH did not appear to correlate with extent of emaciation in MDR-TB patients.</P>