Search results for "Pharmacokinetics"
showing 10 items of 458 documents
Pharmacokinetics and pharmacodynamics of hydroxyethyl starch in hypovolemic pigs; a comparison of peripheral and intraosseous infusion.
1999
Intraosseous (i.o.) infusion is considered a useful technique for the administration of medications and fluids in emergency situations when peripheral intravascular access is not possible. This study investigated the effectiveness of i.o. versus intravenous (i.v.) infusion of hydroxyethyl starch (HES 200/0.5) in hypovolemic pigs. Twenty-three pigs (8- to 9-week-old) were anaesthesized, instrumented and blood was withdrawn (25-30 ml/kg) to50 mmHg mean arterial pressure (MAP). The animals were left untreated in haemorrhage for 30 min. Relevant haemodynamic parameters were monitored and blood samples were collected for blood gas and HES concentration analysis. Infusion of HES via i.v. or i.o. …
On the applicability of [18F]FBPA to predict L-BPA concentration after amino acid preloading in HuH-7 liver tumor model and the implication for liver…
2017
Abstract Introduction In recent years extra-corporal application of boron neutron capture therapy (BNCT) was evaluated for liver primary tumors or liver metastases. A prerequisite for such a high-risk procedure is proof of preferential delivery and high uptake of a 10 B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [ 18 F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [ 10 B]L-BPA. Methods Tumor bearing mice (hepatocellular carcinoma cell line, HuH-7) were either subject of a [ 18 F]FBPA-PET scan with subsequent measurement of radioactivity content in extracted organs using a gamma counter or injecte…
Characterization of intestinal absorption of C -glycoside flavonoid vicenin-2 from Lychnophora ericoides leafs in rats by nonlinear mixed effects mod…
2015
Vicenin-2 (apigenin-6,8-di-C-β-d-glucopyranoside) is present in hydroalcoholic extracts of the Brazilian species Lychnophora ericoides Mart., Asteraceae, leaves, and the biological effects of this compound have been demonstrated including anti-inflammatory, antioxidant and anti-tumor effects in rat models. Given the potential of this compound as a pharmacological agent, the aims of this investigation were to evaluate the extent of intestinal absorption of vicenin-2, and to determine the intestinal permeation profile using an in situ single-pass intestinal perfusion technique. A validated HPLC–UV method was applied to measure the amount of unabsorbed vicenin-2 in the gut after an oral admini…
O26 Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young Inf…
2019
BackgroundIn the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates.MethodsA ‘meta-model’ using NONMEM with 4894 concentrations from 1631 neonates was built and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming at reaching a target AUC0-24 of 400 mg*h/L at steady state in at least 80% of neonates.ResultsA two-compartment model best fitted the data. Current weight, post-menstrual age (PMA) and serum creatinine were the significant covariates for clearance (CL). After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg twice dail…
In vitro glucuronidation of 7-hydroxycoumarin derivatives in intestine and liver microsomes of Beagle dogs
2019
Beagle dog is a standard animal model for evaluating nonclinical pharmacokinetics of new drug candidates. Glucuronidation in intestine and liver is an important first-pass drug metabolic pathway, especially for phenolic compounds. This study evaluated the glucuronidation characteristics of several 7-hydroxycoumarin derivatives in beagle dog's intestine and liver in vitro. To this end, glucuronidation rates of 7-hydroxycoumarin (compound 1), 7-hydroxy-4-trifluoromethylcoumarin (2), 6-methoxy-7-hydroxycoumarin (3), 7-hydroxy-3-(4-tolyl)coumarin (4), 3-(4-fluorophenyl)coumarin (5), 7-hydroxy-3-(4-hydroxyphenyl)coumarin (6), 7-hydroxy-3-(4-methoxyphenyl)coumarin (7), and 7-hydroxy-3-(1H-1,2,4-t…
External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical set…
2012
AimsVancomycin is one of the most evaluated antibiotics in neonates using modeling and simulation approaches. However no clear consensus on optimal dosing has been achieved. The objective of the present study was to perform an external evaluation of published models, in order to test their predictive performances in an independent dataset and to identify the possible study-related factors influencing the transferability of pharmacokinetic models to different clinical settings.MethodPublished neonatal vancomycin pharmacokinetic models were screened from the literature. The predictive performance of six models was evaluated using an independent dataset (112 concentrations from 78 neonates). T…
Effect of cytochrome P450 inhibitors (diethyl dithiocarbamate, ketoconazole and grapefruit juice) on the pharmacokinetics of all-trans-retinoic acid.
2004
Diethyl dithiocarbamate (DEDTC) has been reported to be a more powerful inhibitor of all-trans-retinoic acid (ATRA) in vitro metabolism than the well-established cytochrome P450 (CYP) inhibitor ketoconazole (KC). In recent years grapefruit juice (GJ) has been shown to be able to increase the oral bioavailability of several drugs by inhibiting intestinal CYP. This study investigated the in vivo effect of these CYP inhibitors on the pharmacokinetics of ATRA. The latter was administered to rats as a constant-rate intravenous (i.v.) infusion (0.48 mg h(-1) kg(-1)) during 10 h and orally (1.6 mg kg(-1)). DEDTC (320 mg kg(-1) x 2 i.v., 6.4 and 32 mg kg(-1) per os (p.o.)) did not change the ATRA c…
Penetration of 2% cyclosporin eyedrops into human aqueous humour.
1989
The penetration into the eye and the systemic absorption of 2% cyclosporin eye drops were determined by polarisation immunofluorescent assay of cyclosporin in the aqueous humour and plasma of 30 patients at the time of cataract surgery. The results were then compared with the corresponding results after oral administration at a dosage of 5 mg/kg/day to three further patients. The maximum intraocular concentration (24 (SD 9) mg/l) was achieved four hours after topical administration. This level was slightly less than that found in aqueous humour (28 (SD 10) mg/l) 12 hours after systemic administration of the drug at a dosage of 5 mg/kg/day. Both these levels are below the minimum therapeutic…
Determination of boron concentration in blood and tissue samples from patients with liver metastases of colorectal carcinoma using Prompt Gamma Ray A…
2010
As part of the studies on Boron Neutron Capture Therapy at the University of Mainz, Germany, a clinical trial has been started, in which our patients suffering from liver metastases of colorectal carcinoma, have been enrolled. Specimens of blood and healthy tissue samples taken from the patients were measured at the PGAA facilities at the HFR in Petten, The Netherlands, and at the FRM II in Munich, Germany. From the measured boron concentrations, pharmacokinetic curves and blood-to-tissue concentration ratios were produced.
A discourse on human hair fibers and reflections on the conservation of drug molecules
1996
A gross discourse on human hair fibers and their formation is presented stressing the various interdisciplinary aspects, such as the morphological, biological, structural and biochemical data considered to be important in the field of hair analysis. An attempt is made to explain the incorporation of drug molecules during hair fiber formation by using the classical concepts of drug absorption based on lipoid theory and the pH-partition hypothesis as well as a modern biological approach on the permeability of cell membranes. In addition to the physiochemical considerations of the transport properties of a particular drug molecule such as a) the lipophilicity, which determines permeability thr…