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Post Dose (post + dose)
Kinds of Post Dose Selected AbstractsORIGINAL RESEARCH,PHARMACOTHERAPY: Hemodynamic Effects of Sildenafil Citrate and Isosorbide Mononitrate in Men with Coronary Artery Disease and Erectile DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2005Graham Jackson ABSTRACT Introduction., Mild hemodynamic effects have been reported with sildenafil citrate therapy. Aim., To compare the hemodynamic effects of sildenafil and isosorbide mononitrate (ISMN) in men with coronary artery disease and erectile dysfunction. Methods., A total of 31 men aged 35 years or older with coronary artery disease (at least 50% narrowing of the left main stem or at least 70% narrowing of any other coronary artery) and erectile dysfunction (receiving medication for erectile dysfunction or scoring less than 26 out of a maximum score of 30 on the erectile function domain questions of International Index of Erectile Function) were randomized to sildenafil 100 mg (n = 10), ISMN 40 mg (n = 11), or placebo (n = 10) in this single-dose multicenter study. Main Outcome Measures., Hemodynamic parameters were measured at baseline, 1, 2, 4, and 6 hours post dose. Results., Compared with baseline, cardiac index increased slightly with sildenafil (0.29 L/min/m2 at 1 hour) and decreased slightly with placebo (,0.12 L/min/m2 at 4 hours) and ISMN (,0.14 L/min/m2 at 1 hour). The stroke volume index increased from baseline at each time point post dose with sildenafil (4.4 mL/m2 at 2 hours), but decreased with ISMN (,5.8 mL/m2 at 1 hour) and placebo (,2.8 mL/m2 at 4 hours). ISMN reduced mean arterial pressure more than sildenafil did (,22 vs. ,10 mm Hg at 2 hours, respectively). Both sildenafil and ISMN increased heart rate (4 vs. 7 beats/minute at 1 hour, respectively) and decreased systemic vascular resistance, but sildenafil produced greater reductions in pulmonary vascular resistance. There were no serious adverse events in the sildenafil group. Conclusions., Sildenafil 100 mg was well tolerated and induced smaller changes in central and peripheral hemodynamic pressures compared with ISMN 40 mg. Moreover, sildenafil selectively reduced pulmonary resistance, which may have clinical importance in pulmonary hypertension. [source] Bioanalytical LC-MS/MS method validation for plasma determination of topiramate in healthy Indian volunteersBIOMEDICAL CHROMATOGRAPHY, Issue 11 2009Dipanjan Goswami Abstract A LC-MS/MS method for plasma topiramate analysis is delineated involving least number of healthy volunteers. Topiramate and amlodipine internal standard (IS) were extracted by simple centrifuge-coupled solid-phase extraction and reverse-phase chromatographic separation was performed on an Ascentis C18 column. Turbo-spray negative-ion mode multiple-reaction monitoring was selected for mass pair detection at m/z 338.3 , 78.0 and m/z 407.3 , 295.5 for analyte and IS respectively. The method showed a dynamic linearity range from 10.4 to 2045.0 ng/mL, lower limit of quantitation achieved at 10.4 ng/mL and finally a mass spectrometric total run time of within 2.5 min for human sample analysis. Bioequivalence was assessed successfully using this fully validated method on 16 fasted Indian male subjects with 25 mg topiramate tablet administration. An appropriate study design describes plasma samples collection up to 216 h post dose in two periods, separated by a 28 day washout period. The challenge of half-life matching for test and reference drug was achieved with 73.43 ± 9.68 and 73.06 ± 14.03 h, respectively, and intra-subject coefficient of variation achieved within 11% for AUCs and Cmax evaluated by non-compartmental pharmacokinetic analysis. The results of LCMS topiramate complete method validation supported by pharmacokinetic study have not been published before, and are presented and discussed for the first time in this article. Copyright © 2009 John Wiley & Sons, Ltd. [source] Does stereoselective lymphatic absorption contribute to the enantioselective pharmacokinetics of halofantrine In Vivo?BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2003David M. Shackleford Abstract Halofantrine (Hf) is a chiral, lipophilic phenanthrene methanol antimalarial which exhibits both enantioselective plasma pharmacokinetics and extensive lymphatic absorption when administered postprandially. In order to determine whether enantioselective lymphatic absorption contributes to the previously reported enantioselective pharmacokinetics of Hf, lymph samples collected from thoracic duct-cannulated dogs dosed with racemic Hf (100 mg, administered postprandially) were assayed with a chiral HPLC method capable of quantifying the relative amounts of (+)- and (,)-Hf. During the period when the majority (>95%) of Hf transport into lymph occurred (0,5 h post dose), essentially equal amounts of the two enantiomers were present in the intestinal lymph. At later times (e.g. 5,12 h post dose), there was a steady increase in the fraction of (+)-Hf present in lymph. The trends evident at later time points most likely reflect an increase in the proportion of (+)-Hf present in systemic blood, (resulting from enantioselective systemic metabolism) and a corresponding increase in (+)-Hf in the thoracic lymph by equilibration of drug across blood and lymphatic capillaries, as opposed to enantioselective lymphatic transport per se. This study was the first to examine the possibility of stereoselectivity in lymphatic transport, however, the data suggest that drug absorption (at least in the case of halofantrine) via the intestinal lymphatics is not enantioselective. Copyright © 2003 John Wiley & Sons, Ltd. [source] Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalationBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2002Osama Aswania Abstract The relative lung and systemic bioavailability of sodium cromoglycate following inhalation by different methods have been determined using a urinary excretion pharmacokinetic method. On three separate randomised study days, 7 days apart, subjects inhaled (i) 4×5 mg from an Intal® metered dose inhaler (MDI), (ii) 4×5 mg from an MDI attached to a large volume spacer (MDI+SP) and (iii) 20 mg from an Intal Spinhaler® (DPI). Urine samples were provided at 0, 0.5, 1, 2, 5 and 24 h post dose. The mean (S.D.) amount of sodium cromoglycate excreted in the urine during the first 30 min post inhalation was 38.1 (27.5), 222.3 (120.3) and 133.1 (92.2) ,g following MDI, MDI+SP and DPI, respectively. The mean ratio (90% confidence interval) of these amounts excreted in the urine over the first 30 min for MDI+SP vs MDI, DPI vs MDI and MDI+SP vs DPI was 801.0 (358.0, 1244; p<0.002)%, 457.0 (244.0, 670.0; p<0.02)% and 262.4 (110.2, 414.5)%, respectively. Similarly for the 24 h cumulative amount of sodium cromoglycate excreted over the 24 h post inhalation the ratios were 375.4 (232.9, 517.9; p<0.005)%, 287.5 (183.4, 391.6; p<0.02)% and 211.4 (88.3, 334.5)%, respectively. The results highlight better lung deposition of sodium cromoglycate from a metered dose inhaler attached to a large volume spacer. Copyright © 2002 John Wiley & Sons, Ltd. [source] Intranasal absorption of sumatriptan and naratriptan: no evidence of local transfer from the nasal cavities to the brain arterial blood in male ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2001Niels Einer-Jensen Abstract Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. This model was used to investigate whether the antimigraine 5HT1B/1D receptor agonists sumatriptan and naratriptan may also be transferred by the system. The ratio of ,head':,heart' plasma concentrations obtained from two carotid catheters after intranasal administration was not different from 1.00 for either compound, and thus, there was no experimental evidence of a preferential local transfer of drug from the nose to the carotid artery circulation. However, plasma concentrations increased from the first minute after intranasal dosing suggesting that sumatriptan and naratriptan are absorbed into the general systemic circulation from the nasal cavity in rats in a first-order fashion with no lag time. This is consistent with the clinical onset of efficacy of sumatriptan after an intranasal dose which occurs as early as 15 min post dose. Copyright © 2001 John Wiley & Sons, Ltd. [source] Plethysmography and impulse oscillometry assessment of tiotropium and ipratropium bromide; a randomized, double-blind, placebo-controlled, cross-over study in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2006D. Singh Aims Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy subjects. Methods Single doses of tiotropium bromide (Tio) 54 and 18 mcg, ipratropium bromide (IB) 40 mcg and placebo were administered. Specific conductance (sGaw), total lung capacity (TLC), inspiratory capacity (IC) and residual volume (RV) were measured using plethysmography, while IOS measured resistance (R5,25) and reactance (RF and X5). Pulmonary function was measured for 26 h post dose. Results Tio caused significant improvements in sGaw, forced expiratory voume in 1 s (FEV1), maximum mid-expiratory flow (MMEF) and R5,R25 at time points up to 26 h, with no clear differences between doses. IB improved the same parameters, but only up to 8 h. The weighted mean change (0,24 h) caused by Tio 54 mcg compared with placebo for FEV1 was 240 ml (95% confidence interval 180, 300), while for sGaw the ratio of geometric means (Tio compared with placebo) was 1.35 (1.28, 1.41). Neither drug caused consistent statistically significant changes in RF, forced vital capacity, TLC or IC over 26 h. RV was significantly improved from 8 to 24 h by Tio 54 mcg only. Conclusions In addition to spirometry, IOS resistance measurements and sGaw can distinguish between the effects of long- and shortacting anticholinergic effects in healthy subjects. [source] Pharmacokinetics and pharmacodynamic effects of ABT-627, an oral ETA selective endothelin antagonist, in humansBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2000Marianne C. Verhaar Aims, Endothelins (ETs) may play a role in the pathogenesis of a variety of cardiovascular diseases. The present study was designed to investigate the pharmacokinetic and pharmacodynamic effects of the orally active ETA selective receptor antagonist ABT-627 in healthy humans. Methods, Healthy volunteers were included in two studies with cross-over design. Subjects received single or multiple dose (an 8 day period) administration of oralABT-627 or matched placebo, in a dose range of 0.2,40 mg. The pharmacokinetics of ABT-627 were described and its effects on systemic haemodynamics under resting conditions and on forearm vasoconstriction in response to ET-1 were assessed. Results, ABT-627 was generally well tolerated in both studies, with transient headache being the most reported adverse event (in 62%vs 4% during placebo, P < 0.05, for Study 1 and in 42%vs 60%, P = 0.2, for Study 2). ABT-627 was rapidly absorbed, reaching maximum plasma levels at ,,1 h post dose. Single dose ABT-627, at a dose of 20 and 40 mg, inhibited ET-1 induced forearm vasoconstriction at 8 h post dose. Eight days ABT-627 treatment, at a dose level of 5 mg and above, also effectively blocked forearm vasoconstriction to ET-1. ABT-627 caused a significant reduction in peripheral resistance as compared with placebo (16 ± 1 vs 19 ± 1, 18 ± 2 vs 23 ± 3, 15 ± 1 vs 17 ± 1 AU at 1, 5, 20 mg in Study 2) with only a mild decrease in blood pressure (79 ± 2 vs 84 ± 3, 80 ± 4 vs 90 ± 5, 75 ± 3 vs 79 ± 1 at 1, 5, 20 mg in Study 2). ABT-627 caused a moderate dose-dependent increase in circulating immunoreactive ET levels (a maximal increase of 50% over baseline at the 20 mg dose level). Conclusions, The oral ETA receptor blocker ABT-627 is well tolerated, rapidly absorbed, effectively blocks ET-1 induced vasoconstriction and causes a decrease in total peripheral resistance and mean arterial pressure. Our data suggest that ABT-627 may be a valuable tool in treatment of cardiovascular disease. [source] | ||||||||||