Search results for "Pharmaceutical Preparation"
showing 10 items of 213 documents
Isoenzyme-specific phosphorylation of cytochromes P-450 and other drug metabolizing enzymes.
1987
Abstract A series of fourteen cytochrome P-450 isoenzymes was treated with three different protein kinases and found to devide into isoenzymes phosphorylated (i) by both the cyclic AMP-dependent kinase and the calcium-phospholipid-dependent kinase (P-450 PB 3a and PB 2e), (ii) by none of these kinases (P-450 PB 1b, MC 1b, UT 1, and thromboxane synthase), and (iii) by either the cyclic AMP-dependent kinase (P-450 LM 2, PB 2d, and PB 3b) or the calcium-phospholipid-dependent kinase (P-450 PB 1a, PB 2a, MC 1a, LM 3c, and LM 4). Other components of the monooxygenase system, cytochrome P-450 reductase, cytochrome b5, cytochrome b5 reductase as well as microsomal epoxide hydrolase, were poor subs…
Coordinated induction of drug transporters and phase I and II metabolism in human liver slices
2008
Although regulation of phase I drug metabolism in human liver is relatively well studied, the regulation of phase II enzymes and of drug transporters is incompletely characterized. Therefore, we used human liver slices to investigate the PXR, CAR and AhR-mediated induction of drug transporters and phase I and II metabolic enzymes. Precision-cut human liver slices were incubated for 5 or 24 h with prototypical inducers: phenobarbital (PB) (50 mu M) for CAR, beta-naphthoflavone (BNF) (25 mu M) for AhR, and rifampicin (RIF) (10 mu M) for PXR, and gene expression of the phase I enzymes CYP1A1, 1A2, 3A4, 3A5, 2136, 2A6, the phase II enzymes UGT1A1 and 1A6, and the transporters MRP2, MDR1, BSEP, …
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4: Prediction accuracy and software comparisons with…
2020
Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption i…
Analysis of drugs including illicit and new psychoactive substances in oral fluids by gas chromatography-drift tube ion mobility spectrometry
2021
Abstract In this study, a gas chromatograph (GC) has been coupled to a drift tube ion mobility spectrometer (IMS) in order to develop an analytical procedure for the determination of psychoactive substances in oral fluids. Working parameters, including the GC-IMS interface ones, were adjusted in order to obtain sensitive and robust signals. A volume of 500 μL of oral fluid was extracted with 250 μL chloroform and, after centrifugation, were injected into the GC-IMS system. Amphetamine, methylone, α-PVP, ketamine, lidocaine, MPHP, cocaine, THJ-2201, and 5F-ADB were employed as model compounds, providing limits of detection from 6 to 15 μg L−1 and recoveries from 70 to 115% for field oral flu…
Chiral separation of bupivacaine enantiomers by capillary electrophoresis partial-filling technique with human serum albumin as chiral selector
2004
Abstract Capillary electrophoresis (CE) is a powerful technique for enantiomer separations due to its intrinsic high separation efficiencies, speed of analysis, low reagent consumption and small sample requirements. However, some chiral selectors present strong background UV absorption providing high detection limits. The present paper deals with the application of the partial-filling technique to the separation of bupivacaine enantiomers by capillary electrophoresis using human serum albumin (HSA) as chiral selector. In this procedure the cationic surfactant cetyltrimethylammonium bromide (CTAB) was used as a dinamic capillary coating in order to reduce the electro-osmotic flow and detect …
Use of micellar mobile phases for the chromatographic determination of clorazepate, diazepam, and diltiazem in pharmaceuticals
2001
An ODS-2 column, a micellar mobile phase of high elution strength containing 0.1M sodium dodecyl sulfate and 3% (v/v) butanol, and ultraviolet detection at 230 nm are used for the determination of either of two benzodiazepines (clorazepate and diazepam) and a benzothiazepine (diltiazem) in pharmaceuticals. The procedure is shown to be competitive against conventional chromatography with methanol-water mobile phases, especially for diltiazem. The composition of the micellar mobile phase is selected using a predictive strategy based on an accurate retention model and assisted by computer simulation. Calibration graphs are linear at least in the 2.5 to 20 microg/mL, 4 to 20 microg/mL, and 5 to…
Induction of Human P-Glycoprotein in Caco-2 cells: Development of a Highly Sensitive Assay System for P-Glycoprotein-Mediated Drug Transport
2006
The aim of this work is to develop a highly sensitive assay system for P-gp-mediated transport by using two methods, induction of P-gp and short-term culture of Caco-2 cells. To induce P-gp in Caco-2 cells, cells were cultured in vinblastine-containing medium. The mRNA level of P-gp was approximately 7-fold higher in Caco-2 cells cultured with vinblastine (P-gp-induced Caco-2 cells) than in control cells. Western blot analysis showed a significant increase in P-gp expression. After cell differentiation, the mRNA level of P-gp was downregulated, however, P-gp-induced Caco-2 cells still possessed a 5.6-fold higher mRNA level of P-gp compared to control cells. Polarized transport of substrate …
Direct injection of physiological fluids in micellar liquid chromatography
2000
Abstract Micellar liquid chromatography (MLC), which uses mobile phases of surfactants above the critical micellar concentration, provides a solution to the direct injection of physiological samples by solubilizing the protein components, and coating the analytical column with surfactant monomers to avoid clogging. A review showing the advantages and limitations of this technique over other chromatographic techniques used in drug analysis, working protocols, and examples of application is presented. The possibility of direct sample introduction simplifies and greatly expedites the treatments with reduced cost, improving the accuracy of the procedures. Surfactant monomers and micelles appear…
Intestinal drug efflux: formulation and food effects
2001
The intestine, primarily regarded as an absorptive organ, is also prepared for the elimination of certain organic acids, bases and neutral compounds depending on their affinity to intestinal carrier systems. Several of the transport systems known to mediate efflux in the major clearing organs--liver and kidney--are also expressed in the intestine. Examples of secretory transporters in the intestine are P-glycoprotein, members of the multidrug resistance associated protein family, breast cancer resistance protein, organic cation transporters and members of the organic anion polypeptide family. In this communication, the P-glycoprotein mediated intestinal secretion of talinolol, a model compo…
Predictability of drug encapsulation and release from propylene carbonate/PLGA microparticles.
2020
Abstract Key parameters for microparticle-based parenteral depot formulation development are entrapment efficiency and sustained drug release, which both depend on the intermolecular affinity of the components. Here, partial solubility parameters were evaluated as descriptors for 21 drug substances and 3 polymers in propylene carbonate (PC). Out of these 21 drug substances, eight BCS class II substances (celecoxib, clotrimazole, erythromycin, ibuprofen, indomethacin, itraconazole, lopinavir and ritonavir) were encapsulated using PLGA (Poly(DL-lactide-co-glycolide)) as polymer matrix and PC as a polar aprotic solvent in order to assign microparticle properties to potential affinity-related i…