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Washout Interval (washout + interval)
Selected AbstractsTiclopidine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2004Application to bioequivalence study Abstract A rapid, sensitive and specific method to quantify ticlopidine in human plasma using clopidogrel as the internal standard (IS) is described. The analyte and the IS were extracted from acidified plasma by liquid,liquid extraction using diethyl ether,hexane (80 : 20, v/v). The extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC/MS/MS). Chromatography was performed isocratically on a Jones Genesis C8 4 µm analytical column (150 × 4.1 mm i.d.). The method had a chromatographic run time of 3.0 min and a linear calibration curve over the range 1.0,1000 ng ml,1 (r2 > 0.999427). The limit of quantification was 1.0 ng ml,1. This HPLC/MS/MS procedure was used to assess the bioequivalence of two ticlopidine 250 mg tablet formulations (ticlopidine test formulation from Apotex do Brasil, Brazil, and Ticlid from Sanofi-Synthelabo, standard reference formulation). A single 250 mg dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for Cmax and area under the curve ratios were all inside the 80,125% interval proposed by the US Food and Drug Administration, it was concluded that ticlopidine formulation from Apotex do Brasil is bioequivalent to Ticlid formulation with respect to both the rate and the extent of absorption. Copyright © 2004 John Wiley & Sons, Ltd. [source] Inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated pregnant human myometriumACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2005K. Yildiz Background:, In this study, we investigated the inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated human myometrium. Methods:, Following delivery of the infant and placenta, a small segment of myometrium was excised from the upper incisional surface of the lower uterine segment and 20 strips, randomly assigned into two groups (n = 10), were obtained from 20 non-laboring term parturients. The study protocol consisted of a 60-min period of spontaneous contractions, control recording with oxytocin 2 × 109 m (10-min period), washout interval of 10 min, volatile administration (three times per 15-min period) of 0.5, 1 and 2 minimum alveolar concentration (MAC), response to oxytocin (10-min period), a further washout interval (10-min period) and subsequent control recording with oxytocin without anesthetics. Results:, After oxytocin administration, the frequency and amplitude of contractions increased (P < 0.05) and the duration decreased (P < 0.05). The frequency and amplitude of contractions induced with oxytocin decreased significantly at 0.5, 1 and 2 MAC of desflurane and sevoflurane (P < 0.05). The amplitude of contractions was significantly different at 1 MAC between the two groups (P < 0.05). The duration of contractions at 2 MAC decreased in both groups (P < 0.05). Conclusions:, Desflurane and sevoflurane at 0.5, 1 and 2 MAC inhibit the frequency and amplitude of myometrial contractions induced with oxytocin in a dose-dependent manner. However, desflurane inhibits the amplitude less than sevoflurane at 1 MAC. We suggest that 0.5 MAC of both agents and 1 MAC of desflurane may be safely used in the presence of oxytocin following delivery of the infant and placenta during Cesarean section without fear of uterine atony and hemorrhage. [source] Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability studyBIOMEDICAL CHROMATOGRAPHY, Issue 7 2010Ronilson Agnaldo Moreno Abstract In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether,dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5,mm NH4OH on a Gemini Phenomenex C8 5,,m column (50 × 4.6,mm i.d.) in 5.0,min/run. The method fitted to a linear calibration curve (0.05,10,ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0,mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine®, Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for Cmax and AUC ratios were all within the 80,125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption. Copyright © 2009 John Wiley & Sons, Ltd. [source] Amlodipine bioequivalence study: quantification by liquid chromatography coupled to tandem mass spectrometryBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2001M. Carvalho Abstract Objective,To assess the bioequivalence of two amlodipine tablet formulations (Amlodipine® 5 mg tablet from Merck S.A. Indústrias Químicas, Brazil as test formulation and Norvasc® 5 mg tablet from Laboratórios Pfizer Ltd., Brazil as reference formulation) in 24 healthy volunteers of both sexes. Methods,The study was conducted using an open, randomized two-period crossover design with a 4-week washout interval. Plasma samples were obtained over a 144 h period. Plasma amlodipine concentrations were analyzed by combined liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the amlodipine plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC0,inf and Cmax. The statistical interval proposed was 80,125% according to the US Food and Drug Administration Agency. Results,The limit of quantification was 0.1 ng/ml for plasma amlodipine analysis. The geometric mean and the 90% confidence interval (CI) test/reference ratios were 101.2 (92.9,110.2%) for AUClast, 99.6 (91.5,108.4%) for AUC0,inf and 98.5 (89.0,109.1%) for Cmax. Conclusion,Since the 90% CI for AUClast, AUC0,inf and Cmax ratios were within in the 80,125% interval proposed by the US FDA, it was concluded that Amlodipine® 5 mg tablet (test formulation) was bioequivalent to Norvasc® 5 mg tablet, in terms of both rate and extent of absorption. Copyright © 2001 John Wiley & Sons, Ltd. [source] The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010R. H. HUNT Aliment Pharmacol Ther,31, 648,657 Summary Background, Racemic tenatoprazole 40 mg/day provides more prolonged acid suppression than esomeprazole 40 mg/day. Aim, To compare pharmacodynamic and pharmacokinetic profiles of tenatoprazole and esomeprazole. Methods, A single-centre, double-blind, double-dummy, randomized, 4-way, cross-over study was conducted in 32 healthy male subjects. S-tenatoprazole-Na 30, 60 or 90 mg, or esomeprazole 40 mg was administered once daily for 5 days with 10-day washout intervals. The 24-h intragastric pH was recorded at baseline and on day 5 of each period. Results, On day 5, median pH (5.34 ± 0.45 and 5.19 ± 0.52 vs. 4.76 ± 0.82, respectively, P < 0.002) and percentage time with pH > 4 (80 ± 11 and 77 ± 12, vs. 63 ± 11 respectively, P < 0.0001) for 24-h were higher with S-tenatoprazole-Na 90 mg and 60 mg than esomeprazole. In nocturnal periods, S-tenatoprazole-Na 90 mg, 60 mg and 30 mg were superior to esomeprazole with regard to median pH (5.14 ± 0.64, 4.94 ± 0.65, 4.65 ± 0.86 and 3.69 ± 1.18 respectively, P < 0.0001) and percentage time with pH > 4 (77 ± 12, 73 ± 17, 64 ± 17 and 46 ± 17 respectively, P < 0.0001). Proportion of subjects with nocturnal acid breakthrough with S-tenatoprazole-Na 90 mg, 60 mg and 30 mg was significantly less than with esomeprazole (54.8, 43.3, 56.7 and 90.3 respectively, P < 0.04). The proportion of subjects with >16 hrs with pH >4 was significantly higher with S-tenatoprazole-Na 90 mg and 60 mg than with esomeprazole (87.1%, 83.3% and 41.9% respectively, P < 0.02). Conclusions, S-tenatoprazole-Na produced significantly greater and more prolonged dose-dependent 24-h and nocturnal acid suppression than esomeprazole. S-tenatoprazole-Na may provide greater clinical efficacy compared with current PPIs for patients with ineffective once-daily therapy. [source] | |||||||||||||