Drugs online research references
Z Geburtshilfe Perinatol. 1981 Dec;185(6):313-20.
[Investigations in animal experiments into the influence of the beta-1-selective blocking agent metoprolol on the cardiovascular and metabolic side effects of the tocolytic fenoterol]
[Article in German]
Strigl R, Pfeiffer U, Sagerer M, Birk M, Aschenbrenner G, Erhardt W, Kohler W, Blumel G.
The influence of the highly selective beta-1-adrenergic blocker Metoprolol on cardiovascular and metabolic side effects of the beta-mimetic Fenoterol, used for labour inhibition, was investigated in anesthetized mongrel dogs. In a dosage of 1.5 microgram/kg BW/min Metoprolol antagonized the positive inotropic and chronotropic cardiac effects of Fenoterol (0.06 microgram/kg BW/min) thus compensating the impaired energetic balance of the myocardium. As expected, there was no influence on the beta-mimetic mediated metabolic alterations. Taking into account its pharmacologic actions, the additional application of Metoprolol in labour inhibition with beta-mimetics seems to be advantageous. On account of the proven results a reduction of the more or less considerable missensations and a cardioprotective effect may be expected.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7200286&dopt=Abstract
Arch Biochem Biophys. 1996 Apr 1;328(1):143-50.
Functional high level expression of cytochrome P450 CYP2D6 using baculoviral expression systems.
Paine MJ, Gilham D, Roberts GC, Wolf CR.
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Scotland.
Cytochrome P-450 CYP2D6 plays a central role in the metabolism of many widely used therapeutic drugs including beta-adrenergic antagonists, antiarrhythmics, and tricyclic antidepressants. Recombinant baculoviruses have been constructed containing the full-length human CYP2D6 cDNA and used to express CYP2D6 in Spodoptera frugiperda (Sf9) cells. High levels of recombinant protein have been produced using either polyhedrin or basic protein promoters (0.05-0.20 nmol/mg cell protein; 0.05-0.15 nmol/liter). The enzyme is catalytically active toward CYP2D6 substrates such as bufuralol and metoprolol. In order to optimize catalytic activity human reductase was coexpressed with CYP2D6 in Sf9 cells; reductase activity was in the region of 1000-1500 units per mg cell protein, while spectrally active CY2D6 was in the range 10-20 pmol/mg cell protein. The K(m) and K(cat) values for bufuralol metabolism were estimated as 4.7 microM and 12.23 min-1, respectively. The use of the conventional very late promoters such as the polyhedrin promoter generate a large proportion of inactive CYP2D6. The problem was to a degree circumvented using the "late" basic promoter which is active earlier in the baculovirus infection cycle. The yield of functional CYP2D6 was at least as high as with very late promoters, but the proportion of inactive protein was reduced. Bufuralol hydroxylase activity could be measured directly by HPLC analysis of cell culture media supplemented with bufuralol, and we have developed a plate assay system which provides a simple method for the analysis of drug metabolism reactions using Sf9 cells. Expression using baculovirus provides a valuable source of functional CYP2D6 for work aimed at elucidating the structure and function of the enzyme.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8638923&dopt=Abstract
Pharm Dev Technol. 1996 Dec;1(4):343-55.
The role of intra- and extragranular microcrystalline cellulose in tablet dissolution.
Li JZ, Rekhi GS, Augsburger LL, Shangraw RF.
University of Maryland at Baltimore, Department of Pharmaceutical Sciences, School of Pharmacy 21201-1180, USA.
The objective of this study was to examine the influence of intra- and extragranular microcrystalline cellulose (MCC) on drug dissolution from tablets made by high-shear granulation. Granulations were made in a Littleford Model W-10-B (10-liter) mixer and dried in a fluid bed dryer (Niro Inc.). A Plackett-Burman screening design and 2(3) factorial design were employed to study how drug type, MCC (intra- or extra-), filler type (lactose or dicalcium phosphate), disintegrant type (sodium starch glycolate or croscarmellose sodium) and level, proportion of magnesium stearate, and impeller speed affect tablet hardness, disintegration time, and dissolution. Two model drugs were chosen based on their solubility: metoprolol tartrate (solubility > 1000 mg/ml) and hydrochlorothiazide (solubility = 1.05 mg/ml). Tablets were compressed to the same target weight (dose) and similar tablet hardness. In some cases, dissolution testing was also carried out on the loose granules. The intra-extragranular distribution of MCC was found critical to the compactibility and initial dissolution rates from these tablets. Intragranular MCC reduced drug dissolution, the effect being most marked in the case of the slightly soluble hydrochlorothiazide. For formulations containing intragranular MCC, the granulating fluid level on tablet dissolution was also important, since an increase in fluid level resulted in slower drug dissolution from both the loose granules and the tablets compressed from them. Conversely, extragranular MCC tended to increase both dissolution rates and compactibility. It may be concluded that the appropriate distribution of MCC between and within granules may optimize both dissolution and compactibility without changing overall tablet composition.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9552318&dopt=Abstract
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