Search results for "Pharmacokinetic"
showing 10 items of 474 documents
Dose-dependent metabolism and hepatic distribution of phenprocoumon in rats
1988
The dose-dependency of phenprocoumon disposition was determined in rats by iv administration of 0.1 and 1.0 mg/kg doses to separate groups of animals. The intrinsic clearance (unbound clearance) was 33% lower in the animals given 1.0 mg/kg dose than in the animals given 0.1 mg/kg dose. The apparent unbound volume of distribution was 55% lower and the elimination rate constant 54% higher in the high dose group than in the lower dose group. Binding of phenprocoumon to liver showed saturability with a two- to threefold higher apparent unbound fraction of phenprocoumon in liver in animals given the high dose in comparison to animals given the low dose.
Factors responsible for interindividual differences in the dose requirement of phenprocoumon
1987
The total and unbound plasma concentrations of phenprocoumon and the prothrombin complex activity were determined in 51 patients on phenprocoumon. A 7-fold difference in the dosing rate (10-70 micrograms/kg/day) was required to maintain the prothrombin complex activity at 11-30% of normal. The variation in dosing requirement was mainly due to interindividual differences in the intrinsic clearance of phenprocoumon and only to a minor degree to differences in sensitivity to it. On average patients with myocardial infarction required only 2/3 of the daily dose of phenprocoumon of post cardiac surgery patients and patients with thrombosis and emboli. That difference appeared to be due to higher…
Sex-related Differences in Disposition and Response to Phenprocoumon in Rats
1988
Abstract The pharmacokinetics and the pharmacological response to phenprocoumon have been studied in female and male inbred Lewis-Wistar rats. A significantly lower clearance was found in female than in male rats (7.9 ± 1.4 vs 24.5 ± 2.5 mL h−1 kg−1, respectively; t = 15.09, P < 0.001) as well as a lower apparent volume of distribution (288 ± 46 vs 617 ± 105 mL kg−1; t = 7.58, P < 0.001) and a longer half-life (25.5 ± 3.4 vs 17.5 ± 1.8 h; t = 5.16, P < 0.001). The binding of phenprocoumon was higher in female than in male rats (fu: 0.0096 ± 0.0008 vs 0.0124 ± 0.0007, respectively; t = 6.66, P < 0.001). The total (C) as well as the unbound concentration (Cu) neede…
Posterior compartment of the lower leg reconstruction with free functional rectus femoris transfer after sarcoma resection.
2009
A 72-year-old man with the third recurrence of a low-grade liposarcoma of the right lower leg came to our attention seeking limb-salvage surgery. The tumour was removed en bloc with all the superficial posterior compartment of the leg. Appropriate foot flexion was restored by means of a free-functional rectus femoris musculocutaneous flap harvested from the ipsilateral thigh. The patient was kept on a postoperative splint for 6 weeks. Three months after the operation, clinical and elecromyographic signs of reinnervation were observed. The patient was able to walk, run and climb stairs and no donor-site morbidity was observed. Thigh extension was rated M4, comparable to the contralateral thi…
Vancomycin pharmacokinetics during continuous ambulatory peritoneal dialysis in patients with peritonitis.
2011
The aim of this study was to define a two-compartments pharmacokinetic model and to estimate the pharmacokinetic parameters of IP administered vancomycin in patients with continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis. Ten patients with peritoneal dialysis treatment and peritonitis were prospectively enrolled in the study. The empiric treatment is: vancomycin 2 g every 5-7 days and ceftazidime 1500 mg per exchange, once daily. Pharmacokinetic modeling and parameter calculations were carried out using the nonlinear regression. The mean peritoneal concentration 10 min after the first peritoneal exchange of vancomycin free dialysis liquid was 9.5±7.3 μg/ml, showing tha…
Anticoagulation with argatroban for elective percutaneous coronary intervention: population pharmacokinetics and pharmacokinetic-pharmacodynamic rela…
2010
The synthetic direct thrombin inhibitor argatroban has a rapid onset and offset of anticoagulation. However, there are no data about the pharmacokinetic-pharmacodynamic (PK-PD) relationship of argatroban in patients undergoing contemporary percutaneous coronary intervention (PCI) and no data about other coagulation parameters than activated clotting time (ACT) in this setting. In the ARG-E04-trial, 140 patients were randomly assigned to argatroban (250, 300, or 350 μg/kg as bolus before PCI, followed by 15, 20, or 25 μg/kg/min infusion) or unfractionated heparin (70-100 IU/kg bolus). A 2-compartment model with first-order elimination adequately described the pharmacokinetic profile of argat…
Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resi…
2018
In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Methods Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in bloo…
Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DAL…
2014
The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The followi…
Medroxyprogesterone acetate: steady-state pharmacokinetics bioequivalence of two oral formulations
1989
Two micronized oral formulations of medroxyprogesterone acetate (MPA) (Farlutal and Clinovir) were compared in order to evaluate their relative bioavailability. Sixteen female patients with metastatic breast cancer were entered in a randomized cross-over study on 500-mg MPA tablets repeatedly administered (twice daily for 20 days). At the steady state, similar mean +/- SD serum levels of MPA were obtained (131 +/- 44 ng/ml for Farlutal and 136 +/- 45 ng/ml for Clinovir) and the two formulations proved to be bioequivalent (confidence interval at a significance level of 0.95 = 93%-107%).
Metabolism of n-Butyl Benzyl Phthalate in the Female Wistar Rat. Identification of New Metabolites
1999
International audience; n-Butyl benzyl phthalate (BBP), a plasticizer used in polyvinylchloride (PVC) and other polymers, has been orally administered to female Wistar rats with four doses (150, 475, 780 and 1500 mg/kg body weight/day) for 3 consecutive days. Metabolites recovered in urines were analysed by gas chromatography±mass spectrometry (GC±MS) after 24, 48 and 72 hours. Six metabolites were identi®ed. Mono-n-butyl phthalate (MBuP) and mono-n-benzyl phthalate (MBeP) represented respectively 29± 34% and 7±12 % of the total recovered metabolites. Hippuric acid, the main metabolite of benzoic acid, represented the second major metabolite (51±56%). Phthalic acid, benzoic acid and an o-ox…