Home About us Contact
|
Home About us Contact | ||
|
|
||
Clinical Drug (clinical + drug)
Terms modified by Clinical Drug Selected AbstractsClinical drug interactions in outpatients of a university hospital in ThailandJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2005B. Janchawee PhD Summary Background:, A clinical event is likely to occur in patients receiving a pair of drugs, that have the potential to cause an interaction. The occurrence of a clinical drug,drug interaction in outpatients of university hospitals in Thailand is unknown. Purpose:, To investigate the occurrence of a clinical event associated with drug,drug interactions in outpatients at a Thai university hospital. Methods:, A case,control study was established. The case was a sample group, randomly selected from a 1-year sample of outpatient prescriptions containing ,significance-1' potential drug,drug interactions, whereas the control was from the same year but with no potential drug interactions. Medical records of the cases and the controls were reviewed for an adverse event (AE) using a newly developed review form. The odds ratio of occurrence of the AE between the cases and the controls was determined. The AE was assessed for its possibility of being caused from a drug,drug interaction. Results:, The most common specific AE in both the cases and the controls was cough. An unplanned revisit to outpatient department or emergency room was found to be the most common general AE. The odds ratio of the occurrence of an AE in the cases, compared with the controls, was 1·495 (95% CI: 0·917,2·438). The possibility that the AEs resulted from drug interactions in the case group was nine ,probable' patients and 15 ,possible' patients, whereas that in the control group was eight ,possible' patients. The most common interacting drug pair was isoniazid,rifampin with an increase in serum hepatic enzymes as the corresponding AE. Conclusions:, Despite outpatients receiving drug pairs with a high potential for adverse interactions, the rate of occurrence of clinical drug interaction events was low. [source] In vitro drug interaction between diflunisal and indomethacin via glucuronidation in humansBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2006Yuji Mano Abstract It was reported that the plasma concentration of indomethacin was increased with concomitant oral dosages of diflunisal in humans. Both indomethacin and diflunisal are glucuronidated in humans. The effects of diflunisal on the indomethacin glucuronidation were thus investigated in vitro using human liver microsomes (HLM) and human intestine microsomes (HIM) in order to assess the drug,drug interaction. The glucuronidation of indomethacin in HLM showed atypical kinetics with Km and Ksi values of 210 and 89.5 µM, respectively, while HIM exhibited Michaelis,Menten kinetics with a Km value of 17.4 µM. Diflunisal inhibited the indomethacin glucuronidation in HLM with IC50 values ranging from 100 to 231 µM. In HIM, inhibition of the indomethacin glucuronidation by diflunisal was more potent with IC50 values of 15.2,48.7 µM. When the clinical dose of diflunisal (250 mg b.i.d.) is taken into consideration, it is expected that the diflunisal concentration in the intestine would be higher than the IC50 values for indomethacin glucuronidation in the intestine. These findings suggest that the clinical drug,drug interaction between diflunisal and indomethacin may be at least partly attributable to the inhibition of indomethacin glucuronidation by diflunisal in the intestine. Copyright © 2006 John Wiley & Sons, Ltd. [source] Effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Hyunmi Kim WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Woohwangcheongsimwon suspension has traditionally been used for the treatment and prevention of stroke, hypertension, palpitations, convulsions and unconsciousness in various Asian countries. , Woohwangcheongsimwon suspensions showed an inhibitory effect on CYP2B6 activity in vitro. Two terpenoids, borneol and isoborneol, are major constituents of woohwangcheongsimwon suspension, and show a competitive inhibition of CYP2B6 with Ki values of 9.5 and 5.9 µm, respectively. , Bupropion undergoes metabolic transformation to the active metabolite, 4-hydroxybupropion, primarily via CYP2B6 both in vivo and in vitro. It is often used as a CYP2B6 substrate for clinical drug,drug interaction studies. , Drug interactions may occur between woohwangcheongsimwon suspension and bupropion. WHAT THIS STUDY ADDS , Co-administration with woohwangcheongsimwon suspension did not alter the pharmacokinetics of bupropion or its metabolite, 4-hydroxybupropion. , Dosage adjustment of bupropion is unnecessary in patients concomitantly administered the highest recommended daily dose of woohwangcheongsimwon suspension. AIMS To examine the effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, formed via CYP2B6 in vivo. METHODS A two-way crossover clinical trial with a 2 week washout period was conducted in 14 healthy volunteers. In phases I and II, subjects received 150 mg bupropion with or without woohwangcheongsimwon suspension four times (at ,0.17, 3.5, 23.5 and 47.5 h, with the time of bupropion administration taken as 0 h) in a randomized balanced crossover order. Bupropion and 4-hydroxybupropion plasma concentrations were measured for up to 72 h by LC-MS/MS. Urine was collected up to 24 h to calculate the renal clearance. In addition, the CYP2B6*6 genotype was also analyzed. RESULTS The geometric mean ratios and 90% confidence interval of bupropion with woohwangcheongsimwon suspension relative to bupropion alone were 0.976 (0.917, 1.04) for AUC(0,,) and 0.948 (0.830,1.08) for Cmax, respectively. The corresponding values for 4-hydroxybupropion were 0.856 (0.802, 0.912) and 0.845 (0.782, 0.914), respectively. The tmax values of bupropion and 4-hydroxybupropion were not significantly different between the two groups (P > 0.05). The pharmacokinetic parameters of bupropion and 4-hydroxybupropion were unaffected by woohwangcheongsimwon suspension. CONCLUSIONS These results indicate that woohwangcheongsimwon suspension has a negligible effect on the disposition of a single dose of bupropion in vivo. As a result, temporary co-administration with woohwangcheongsimwon suspension does not seem to require a dosage adjustment of bupropion. [source] A cocaine insensitive chimeric insect serotonin transporter reveals domains critical for cocaine interactionFEBS JOURNAL, Issue 16 2002Sumandeep K. Sandhu Serotonin transporters are key target sites for clinical drugs and psychostimulants, such as fluoxetine and cocaine. Molecular cloning of a serotonin transporter from the central nervous system of the insect Manduca sexta enabled us to define domains that affect antagonist action, particularly cocaine. This insect serotonin transporter transiently expressed in CV-1 monkey kidney cells exhibits saturable, high affinity Na+ and Cl, dependent serotonin uptake, with estimated Km and Vmax values of 436 ± 19 nm and 3.8 ± 0.6 × 10,18 mol·cell·min,1, respectively. The Manduca high affinity Na+/Cl, dependent transporter shares 53% and 74% amino acid identity with the human and fruit fly serotonin transporters, respectively. However, in contrast to serotonin transporters from these two latter species, the Manduca transporter is inhibited poorly by fluoxetine (IC50 = 1.23 µm) and cocaine (IC50 = 12.89 µm). To delineate domains and residues that could play a role in cocaine interaction, the human serotonin transporter was mutated to incorporate unique amino acid substitutions, detected in the Manduca homologue. We identified a domain in extracellular loop 2 (amino acids 148,152), which, when inserted into the human transporter, results in decreased cocaine sensitivity of the latter (IC50 = 1.54 µm). We also constructed a number of chimeras between the human and Manduca serotonin transporters (hSERT and MasSERT, respectively). The chimera, hSERT1,146/MasSERT106,587, which involved N-terminal swaps including transmembrane domains (TMDs) 1 and 2, was remarkably insensitive to cocaine (IC50 = 180 µm) compared to the human (IC50 = 0.431 µm) and Manduca serotonin transporters. The chimera MasSERT1,67/hSERT109,630, which involved only the TMD1 swap, showed greater sensitivity to cocaine (IC50 = 0.225 µm) than the human transporter. Both chimeras showed twofold higher serotonin transport affinity compared to human and Manduca serotonin transporters. Our results show TMD1 and TMD2 affect the apparent substrate transport and antagonist sensitivity by possibly providing unique conformations to the transporter. The availability of these chimeras facilitates elucidation of specific amino acids involved in interactions with cocaine. [source] The capillary electrophoresis separation of benzodiazepine drug using dextran sulfate and SDS as running bufferBIOMEDICAL CHROMATOGRAPHY, Issue 3 2004Yoshio Suzuki Abstract Capillary electrophoresis has been applied the analyses of many clinical drugs due to its rapid, high-resolution separation. In this study, electrokinetic chromatography involving the combination of SDS and dextran sulfate, which are synthetic polymers, was examined in order to obtain high resolution. Use of 2% dextran sulfate (10,000 molecular weight), 20 mm SDS running buffer containing boric acid solution (pH 9.2) and a silica capillary (inner diameter of 75 µm, effective length of 50 cm, 57 cm overall length) afforded separation of 10 kinds of benzodiazepines. The detection limit was 0.2 µg/mL; additionally, reproducibilities were de,ned as the peak height and migration time. The average peak height was 5.92% (2.46,17.61), whereas the average migration time was 0.44% (0.18,0.76; n = 5). This separations system can be applied to the analysis and measurement of other pharmaceuticals as well. Copyright © 2004 John Wiley & Sons, Ltd. [source] | |||||||||||||