Search results for "Pharmacokinetic"
showing 10 items of 474 documents
Pharmacokinetic analysis of the interaction between dicoumarol and tolbutamide in man
1976
The effect of repeated administration of tolbutamide on the elimination and anticoagulant action of a single oral dose of dicoumarol 600 mg was studied in four healthy male subjects using a crossover design. In all subjects the plasma concentration of dicoumarol in the postabsorptive phase was lower during concomitant tolbutamide treatment. However, the subjects differed with respect to the elimination kinetics of dicoumarol and the effect of tolbutamide on some of the measured pharmacokinetic paramaters. In two subjects dicoumarol was eliminated by apparent first-order kinetics. Tolbutamide led to a pronounced increase in the elimination rate and a shift in the plasma concentration-respons…
Justification of Biowaiver for Carbamazepine, a Low Soluble High Permeable Compound, in Solid Dosage Forms Based on IVIVC and Gastrointestinal Simula…
2009
The aim of the present study was to use gastrointestinal simulation technology and in vitro-in vivo correlation (IVIVC) as tools to investigate a possible extension of biowaiver criteria to BCS class II drugs using carbamazepine (CBZ) as a candidate compound. Gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus was used. Actual in vitro and in vivo data generated in CBZ bioequivalence studies were used for correlation purposes. The simulated plasma profile, based on the CBZ physicochemical and pharmacokinetic properties, was almost identical with that observed in vivo. Parameter sensitivity analysis (PSA) indicated that the p…
A novel technique for intraduodenal administration of drug suspensions/solutions with concurrent pH monitoring applied to ibuprofen formulations
2019
Characterization of dissolution of solid suspended drug particles in vivo is important for developing biopredictive in vitro tests. Therefore, methods to gain deeper insights into particle dissolution in vivo are needed. The soft Bioperm intubation method, a well established tool for investigation of permeability, absorption, metabolism, and drug interactions at predefined locations in the gastroinstinal tract, was modified. The novel intubation method involved pump-controlled infusion of pharmaceutical suspensions as well as simultaneous pH monitoring. This technique was used in a proof of concept study in healthy humans. Plasma sampling and non-compartmental analysis allowed comparison of…
Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application
1994
Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t1/2 beta), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance…
Postmortem distribution of dihydrocodeine and metabolites in a fatal case of dihydrocodeine intoxication.
1998
A report of a fatal dihydrocodeine ingestion under substitution therapy is given. Quantitation of dihydrocodeine, dihydromorphine, N-nordihydrocodeine, dihydrocodeine-6-, dihydromorphine-6- and dihydromorphine-3-glucuronide was performed simultaneously after solid-phase extraction prior to HPLC analysis, and the analytes were detected using their native fluorescence. Postmortem concentrations of blood samples from different sampling sites as well as from liver, kidney and cerebrum are reported. A hair sample was investigated to prove long-term use of the substitute drug. Site-to-site differences of the analytes from blood samples were very small. The partition behavior of the opioid glucuro…
Pharmacokinetics of triamterene after i.v. administration to man: determination of bioavailability.
1983
With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. …
The tomato sauce making process affects the bioaccessibility and bioavailability of tomato phenolics: A pharmacokinetic study
2013
Tomato sauce is the most commonly consumed processed tomato product worldwide, but very little is known about how the manufacturing process may affect the phenolic composition and bioavailability after consumption. In a prospective randomised, cross-over intervention study, we analysed the plasma and urinary levels of tomato phenolic compounds and their metabolites after acute consumption of raw tomatoes and tomato sauce, enriched or not with refined olive oil during production. Respectively, eleven and four phenolic metabolites were found in urine and plasma samples. The plasma concentration and urinary excretion of naringenin glucuronide were both significantly higher after the consumptio…
Model-based approach to describe G-CSF effects in carboplatin-treated cancer patients.
2013
Granulocyte colony-stimulating factor (G-CSF) is often used in cancer patients receiving cytotoxic drugs to prevent or reduce high grade neutropenia. We propose a pharmacokinetic/pharmacodynamic model to describe myelotoxicity in both G-CSF treated and non-treated patients that shall increase our understanding of G-CSF effects. The model was built from absolute neutrophil counts (ANC) obtained in 375 carboplatin-treated patients, 47 of whom received G-CSF. It includes some prior information on G-CSF taken from the literature. Simulations were performed to understand differences in G-CSF effects and explore the impact of G-CSF formulation. Our model well described the data in all patients. M…
Population pharmacokinetic parameters of vancomycin in critically ill patients.
2006
Summary Background: Intensive care unit patients are a highly heterogeneous population. Accurate dosing for this population requires characterization of the appropriate pharmacokinetic parameters. Objective: To estimate population pharmacokinetic parameters of vancomycin (VAN) in adult critically ill patients and to establish the predictive performance of the resulting model. Patients and method: Fifty critically ill patients with suspected or documented infection with VAN-sensitive micro-organisms were included. Thirty patients and 234 serum concentration–time sets obtained during clinical routine monitoring were used to estimate the pharmacokinetic parameters (group A). An open bicompa…
IVIVC for fenofibrate immediate release tablets using solubility and permeability as in vitro predictors for pharmacokinetics.
2010
The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose-technique. The in vitro determined drug solubility and permeability data were related to the C(max) values observed from two in vivo human studies. Solubility and permeation studies of fenofibrate were conducted in medium simulating the fasted state conditions in the upper jejunum, containing the surfactant compositions of the six formulations at different concentrations. The behavior of all surfactant compositions was characterized by surface tension, dynamic light scattering, and cryo-TEM. The obtained solubility and permeation dat…