11.
Bengtsson, Jörgen, et al.
(författare)
On-line desalting and determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide in microdialysis and plasma samples using column switching and liquid chromatography/tandem mass spectrometry
2005
Ingår i: Rapid Communications in Mass Spectrometry. - : John Wiley & Sons. - 0951-4198 .- 1097-0231. ; 19:15, s. 2116-2122
Tidskriftsartikel (refereegranskat) abstract
A sensitive and reproducible method for the determination of morphine and the metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was developed. The method was validated for perfusion fluid used in microdialysis as well as for sheep and human plasma. A C18 guard column was used to desalt the samples before analytical separation on a ZIC HILIC (hydrophilic interaction chromatography) column and detection with tandem mass spectrometry (MS/MS). The mobile phases were 0.05% trifluoroacetic acid (TFA) for desalting and acetonitrile/5 mM ammonium acetate (70:30) for separation. Microdialysis samples (5 microL) were directly injected onto the system. The lower limits of quantification (LLOQ) for morphine, M3G and M6G were 0.50, 0.22 and 0.55 ng/mL, respectively, and the method was linear from LLOQ to 200 ng/mL. For plasma, a volume of 100 microL was precipitated with acetonitrile containing internal standards (deuterated morphine and metabolites). The supernatant was evaporated and reconstituted in 0.05% TFA before the desalting process. The LLOQs for sheep plasma were 2.0 and 3.1 ng/mL and the ranges were 2.0-2000 and 3.1-3100 ng/mL for morphine and M3G, respectively. For human plasma, the LLOQs were 0.78, 1.49 and 0.53 ng/mL and the ranges were 0.78-500, 1.49-1000 and 0.53-500 ng/mL for morphine, M3G and M6G, respectively.
12.
Berggard, Cecilia, et al.
(författare)
Brainstem levels of transcription factor AP-2 in rat are changed after treatment with phenelzine, but not with citalopram
2005
Ingår i: BMC Pharmacology. - : Springer Science and Business Media LLC. - 1471-2210. ; 5, s. 1-
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: Before therapeutic effect is obtained after treatment with antidepressant drugs, like serotonin selective reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAO-Is) there is an initial lag-period of a few weeks. Neuronal adaptations on a molecular level are supposed to be involved in the initiation of the antidepressant effect. Transcription factor AP-2 is essential for neuronal development and many genes involved in the brainstem monoaminergic systems have binding sites for AP-2 in their regulatory regions. The genotype of the AP-2beta isoform has been associated with e.g. anxiety-related personality traits and with platelet MAO activity. In addition, previous studies have shown that the levels of AP-2alpha and AP-2beta in rat whole brain were decreased after 10 days of treatment with citalopram (SSRI) and imipramine (TCA), and were increased with phenelzine (MAO-I). RESULTS: In the present study, we report that treatment with citalopram for 1, 7 or 21 days did not have effect on the AP-2 levels in rat brainstem. However, after treatment with phenelzine for 1, 7 or 21 days the levels of AP-2alpha and AP-2beta had increased after 7 days, but had returned to control levels at day 21. CONCLUSION: The decrease in AP-2 levels in rat whole brain previously seen after treatment with citalopram does not seem to be localised to the brainstem, it may rather occur in the monoaminergic terminal projection areas. The present data suggest that the increase in AP-2 levels previously seen in rat whole brain after subchronic treatment with phenelzine is located in the brainstem. It cannot, however, be excluded that other brain regions are involved.
13.
Bergström, Christel, 1973-
(författare)
Computational models to predict aqueous drug solubility, permeability and intestinal absorption
2005
Ingår i: Expert opinion on drug metabolism & toxicology. - : Informa Healthcare. - 1742-5255 .- 1744-7607. ; 1:4, s. 613-627
Tidskriftsartikel (refereegranskat) abstract
In the last decade, poor intestinal absorption of candidate drugs intended for oral administration has been identified as a major bottleneck in drug development. Poor intestinal absorption can often be related to poor aqueous solubility and/or poor permeability across the intestinal wall. Other factors, such as poor stability and the metabolism of the compounds, can also decrease the amount of compound absorbed. In an effort to design compounds with enhanced absorption profile, theoretical predictions of solubility and permeability, among other factors, have gained increased interest, and a large number of papers have been published. In this review, the databases and techniques used for the development of in silico absorption models will be discussed. The focus is on aqueous drug solubility, which has become a major problem in drug development.
14.
15.
Boström, Emma, et al.
(författare)
Oxycodone Pharmacokinetics and Pharmacodynamics in the Rat in the Presence of the P-Glycoprotein Inhibitor PSC833
2005
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 94:5, s. 1060-1066
Tidskriftsartikel (refereegranskat) abstract
The objective of this study was to investigate the in vivo influence of the P-glycoprotein (P-gp) inhibitor PSC833 on the plasma pharmacokinetics, total brain concentrations and tail-flick latency of oxycodone in rats. Eight rats each received an infusion of PSC833 or vehicle without PSC833. One hour later, all animals received 0.3 mg/kg oxycodone as a 1-h infusion. Plasma samples were taken, and tail-flick latency was monitored during the infusion and for 2 h thereafter. The brains were collected at the end of the experiment. There were no differences between the two groups in area under the plasma oxycodone concentration-time curve from time zero to infinity, or oxycodone plasma clearance, volume of distribution at steady-state, or half-life. There were no differences in average total brain oxycodone concentrations at 180 min, nor were there any differences in average tail-flick latency for the PSC833 and control groups. In conclusion, coadministration of PSC833 did not alter the plasma pharmacokinetics, brain concentrations, or associated tail-flick latency of oxycodone, indicating that oxycodone is not a P-gp substrate in the rat. This has important clinical implications, as it indicates that oxycodone, unlike some other opioids, will not interact at the blood-brain barrier (BBB) with concomitantly administered P-gp substrates.
16.
17.
Collin, Mattias, et al.
(författare)
Monitor – biology
2005
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:15, s. 1073-1073
Tidskriftsartikel (refereegranskat)
18.
Collin, Mattias, et al.
(författare)
Monitor – biology
2005
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:1, s. 75-77
Tidskriftsartikel (refereegranskat)
19.
Collin, Mattias, et al.
(författare)
Monitor – biology
2005
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:7, s. 530-531
Tidskriftsartikel (refereegranskat)
20.
Collin, Mattias, et al.
(författare)
Monitor – biology
2005
Ingår i: Drug Discovery Today. - 1878-5832. ; 10:17, s. 1201-1203
Tidskriftsartikel (refereegranskat)
