Drugs online research references
J Chromatogr B Biomed Sci Appl. 1997 Aug 15;696(1):69-74.
Efficient high-performance liquid chromatographic assay for the simultaneous determination of metoprolol and two main metabolites in human urine by solid-phase extraction and fluorescence detection.
Chiu FC, Damani LA, Li RC, Tomlinson B.
Department of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
An improved, more efficient method for the determination of metoprolol and its two metabolites in human urine is reported. The simultaneous analysis of the zwitterionic metoprolol acidic metabolite (III, H117/04) with the basic metabolites alpha-hydroxymetoprolol (II, H119/66), metoprolol (I) and guanoxan (IV, internal standard) was achieved employing solid-phase extraction and isocratic reversed-phase HPLC. The analytes were extracted from urine (100 microliters) using C18 solid-phase extraction cartridges (100 mg), and eluted with aqueous acetic acid (0.1%, v/v)-methanol mixture (40:60, v/v, 1.2 ml). The eluents were concentrated (250 microliters) under vacuum, and aliquots (100 microliters) were analysed by HPLC with fluorescence detection at 229 nm (excitation) and 309 nm (emission) using simple isocratic reversed-phase HPLC (Novapak C18 radial compression cartridge, 4 microns, 100 x 5 mm I.D.). Acetonitrile-methanol-TEA/phosphate buffer pH 3.0 (9:1:90, v/v) was employed as the eluent (1.4 ml/min). All components were fully resolved within 18 min, and the calibration curves for the individual analytes were linear (r2 > or = 0.996) within the concentration range of 0.25-40.0 mg/ml. Recoveries for all four analytes were greater than 76% (n = 4). The assay method was validated with intra-day and inter-day variations less than 2.5%.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9300910&dopt=Abstract
Eur J Drug Metab Pharmacokinet. 1991;Spec No 3:146-9.
The role of drug lipophilicity in release from intra-adipose and intramuscular injection sites.
Kadir F, Zuidema J, Pijpers A, Vulto A, Verheijden JH.
University of Utrecht, Department of Pharmaceutics, The Netherlands.
Release rates from intramuscular and intra-adipose injection sites are dependent upon several including injection depth. Little is known about the relationship between drug lipophilicity and transport rate of drugs through adipose and muscle tissue. The principal objective of the present study was to investigate to what extend drug lipophilicity affects release and release rate from adipose tissue. Nine pigs were given intravenous (0.1 mg/kg), intramuscular (0.2 mg/kg) and intra-adipose (0.2 mg/kg) injections of propranolol, alprenolol, carazolol, metoprolol and atenolol. The fraction not-absorbed versus time plots after intramuscular and intra-adipose injection showed a biphasic decline for all model compound with the exception of atenolol being the most hydrophilic drug. This biphasic decline indicates that two different mechanisms may be involved in drug release. Initial release rates after intra-adipose injection were negatively correlated (Kendall's rankorder test) with fat-buffer distribution constants. The extent of release after 24 h could be considered as a characteristic parameter for the second release phase. The amounts released after 24 h were lower for propranolol, alprenolol, carazolol and metoprolol than for atenolol. Incomplete release at 24 h can be explained by the decrease of the solvent drag after absorption of the vehicle is complete.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1687940&dopt=Abstract
Infect Immun. 1994 May;62(5):2046-50.
Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin 6 production in human whole blood.
van der Poll T, Jansen J, Endert E, Sauerwein HP, van Deventer SJ.
Center of Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, University of Amsterdam, The Netherlands.
Sepsis and lipopolysaccharide (LPS) trigger the systemic release of both cytokines and catecholamines. Cytokines are known to be capable of eliciting a stress hormone response in vivo. The present study sought insight into the effect of noradrenaline on LPS-induced release of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6) in human whole blood. Whole blood was incubated with LPS for 4 h at 37 degrees C in the presence and absence of noradrenaline and/or specific alpha and beta antagonists and agonists. Noradrenaline caused a dose-dependent inhibition of LPS-induced TNF and IL-6 production. This effect could be completely prevented by addition of the specific beta 1, antagonist metoprolol, while it was not affected by the alpha antagonist phentolamine. Specific beta-adrenergic stimulation by isoprenaline mimicked the inhibiting effect of noradrenaline on LPS-evoked cytokine production, whereas alpha-adrenergic stimulation by phenylephrine had no effect. Fluorescence-activated cell sorter analysis demonstrated that beta-adrenergic stimulation had no effect on LPS binding to and internalization into mononuclear cells or on the expression of CD14, the major receptor for LPS on mononuclear cells. In acute sepsis, enhanced release of noradrenaline may be part of a negative feedback mechanism meant to inhibit ongoing TNF and IL-6 production.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8168970&dopt=Abstract
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