Pharmacokinetics. In the calculation of plasma concentration summary statistics, values below the lower limit of quantification (LLOQ) will be handled according to the following rules: • If, at a given time point, 50% or less of the plasma concentrations are non- quantifiable (NQ), the geometric mean (gmean), coefficient of variation (CV), gmean ± standard deviation (SD), arithmetic mean, SD and median will be calculated by substituting the LLOQ for values which are NQ. The minimum at that time point will be reported as NQ. • If more than 50%, but not all, of the concentrations are NQ, the gmean, CV, gmean ± SD, arithmetic mean and SD will be reported as not calculable (NC). The minimum and median at that time point will be reported as NQ. • If all the concentrations are NQ, the gmean, arithmetic mean, median, minimum and maximum will be reported as NQ and the CV, gmean ± SD and SD as NC. • If the calculation of the gmean - SD results in a value less than the LLOQ, NQ will be displayed. The plasma concentrations determined using sparse PK sampling scheme, at sampling time points, will be summarised and listed. Box plots will be produced for the PK concentration data on the original raw scale. The geometric mean may also be displayed graphically on the linear and log linear scale.
Pharmacokinetics. The pharmacokinetics of eszopiclone have been investigated in healthy subjects (adult and elderly) and in patients with hepatic disease or renal disease. In healthy subjects, the pharmacokinetic profile was examined after single doses of up to 7.5 mg and after once-daily administration of 1, 3, and 6 mg for 7 days. Eszopiclone is rapidly absorbed, with a time to peak concentration (tmax) of approximately 1 hour and a terminal-phase elimination half-life (t1/2) of approximately 6 hours. In healthy adults, LUNESTA does not accumulate with once-daily administration, and its exposure is dose-proportional over the range of 1 to 6 mg. Absorption And Distribution Eszopiclone is rapidly absorbed following oral administration. Peak plasma concentrations are achieved within approximately 1 hour after oral administration. Eszopiclone is weakly bound to plasma protein (52-59%). The large free fraction suggests that eszopiclone disposition should not be affected by drug-drug interactions caused by protein binding. The blood-to-plasma ratio for eszopiclone is less than one, indicating no selective uptake by red blood cells.
Pharmacokinetics. In patients with congestive heart failure (CHF), Natrecor administered intravenously by infusion or bolus exhibits biphasic disposition from the plasma. The mean terminal elimination half-life (t1/2) of Natrecor is approximately 18 minutes and was associated with approximately 2/3 of the area-under-the-curve (AUC). The mean initial elimination phase was estimated to be approximately 2 minutes. In these patients, the mean volume of distribution of the central compartment (Vc) of Natrecor was estimated to be 0.073 L/kg, the mean steady-state volume of distribution (Vss) was 0.19 L/kg, and the mean clearance (CL) was approximately 9.2 mL/min/kg. At steady state, plasma BNP levels increase from baseline endogenous levels by approximately 3-fold to 6-fold with Natrecor infusion doses ranging from 0.01 to 0.03 (micro)g/kg/min. Elimination
Pharmacokinetics. APADAZ has met the bioequivalence criteria for hydrocodone AUC and Cmax to other immediate- release hydrocodone combination products. Benzhydrocodone was not detectable in plasma after oral administration in clinical studies, indicating that exposure to benzhydrocodone was minimal and transient. Steady state with APADAZ is attained within 24 to 36 hours of dosing. The systemic exposure to hydrocodone from APADAZ increases linearly after administration of single and multiple doses of 2 tablets of APADAZ. Absorption
Pharmacokinetics. Single dose PLGA-curcumin to normal Rats; 5 female and 5 male @ 35mg/kg I.V. Post injection blood sampled for curcumin at 10, 15, 60 minutes, 2 hours, 4 hours, 8 hours 16 hours & 24 hours.
Pharmacokinetics. On occasion, Burrxxxxx-Xxxlcome Company did oxypurinol determinations on blood samples received from physicians concerned about the bioavailability of the drug. In addition, over 200 articles have been identified which contain information on pharmacology and/or pharmacokinetics. These articles and clinical data will be reviewed and summarized for inclusion in the pre-NDA data package.
Pharmacokinetics. C-1- ***Indicates that a portion of the text has been omitted and filed separately with the Commission.
Pharmacokinetics. Local infiltration of EXPAREL results in significant systemic plasma levels of bupivacaine which can persist for 96 hours [See Warnings and Precautions (5.2)]. Systemic plasma levels of bupivacaine following administration of EXPAREL are not correlated with local efficacy.
Pharmacokinetics. For the single dose cohorts, only one whole blood Au concentration was measured above the lloq (1.5 ng/mL), in one subject who received 15 mg Cnm-au8. Consequently, no pk analysis could be done for the sad phase of the study, and the pharmacokinetic analysis was based completely on the multiple dose cohorts. A concentration-time graph for gold plasma concentration at different dose levels of Cnm- au8 is shown in figure 1. Based on pre-specified fit criteria, the elimination t½ could be calculated for only 39% of the subjects and the geometric mean ranged from 277 to 628 hr (11.5 to 26.2 days).Steady-state plasma concentrations for all cohorts, based on the geomet- ric mean whole blood concentrations, were reached by the end of the 2nd week of dosing (Day 14). The geometric mean whole blood concentrations from 1 week onward increased in a dose-related but not dose-proportional manner.This was also the case for days 14 and 21, where the increases in both Cmax and auC(K–MO) were less than dose proportional and the exponents for the power model for both parameters, ~0.43, were considerably lower than 1, indicating a less than dose proportional increase in exposure. Pharmacokinetic param- eters per dose are shown in table 3. In vitro pharmacodynamic experiment Cnm-au8 pretreatment of whole blood or pbmC cultures did not result in an inhibition of tlr9 -driven cytokine release, as investigated in an in vitro experiment. In contrary, higher concentrations of Cnm-au8 enhanced nfκB- (il- 6, il-1β, tnfα),and irf-mediated cyto- kine secretion (figure 2). Based on this outcome, it was decided to not implement a tlr9 challenge as ex vivo pharmacodynamic assay in the clinical study. 60 measuring pharmacodynamics in early clinical drug studies in multiple sclerosis Chapter iv – gold nanopartiCles pharmaCokinetiCs in healthy volunteers 6i discussion This first-in-human study assessed single (sad) and repeated doses (mad) of oral Cnm- au8 over 21 consecutive days. The studied dose ranged from 15 to 90 mg Cnm-au8 and was considered safe and well tolerated. The main reported adverse event was mild self-limiting abdominal pain. Pharmacokinetics were characterised by a long half-life and were less than dose proportional. Gastro-intestinal (gi) adverse events (aes) occurred in 32% of subjects after Cnm-au8 administration. This is comparable to the ae profile of auranofin, an oral gold-containing compound that leads to gi related aes in approximately 40% of casesB?CB. It is impo...
