Drugs online research references
Am J Obstet Gynecol. 1994 Sep;171(3):653-60.
Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer.
Elliott BD, Schenker S, Langer O, Johnson R, Prihoda T.
Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio 78284-7836.
OBJECTIVE: This study compares the human placental transport of glyburide, glipizide, chlorpropamide, and tolbutamide. STUDY DESIGN: The recirculating single cotyledon human placenta model tested maternal-to-fetal transport in term placentas perfused immediately after delivery. Drug levels were measured by high-performance liquid chromatography and liquid scintillation spectrometry, and transport rates were calculated by comparing maternal and fetal concentrations. RESULTS: The transport of these substances differed significantly over a tenfold range (analysis of variance, p < 0.0008). A significant association exists by multiple linear regression between drug transfer and molecular weight, dissociation constant, and the octanol-water partition coefficient (R2 = 0.91, p < 0.0001). CONCLUSIONS: There is significant variability in human placental transfer rates of the oral hypoglycemics, which strongly correlates with molecular properties. These data suggest that less fetal exposure may occur with second-generation sulfonylureas and anticipate that regression models may be useful in selecting agents that minimize placental transport to the fetus.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8092211&dopt=Abstract
J Pharm Pharmacol. 1993 Jul;45(7):671-4.
K(+)-channel blockers and coronary vasoconstriction in guinea-pig perfused hearts in-vitro.
Gwilt M, Orme J, Rourke JD, Henderson CG.
Cardiovascular Department, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
Glibenclamide, glipizide and phentolamine, three drugs which have been reported to block ATP-dependent potassium channels, increased the coronary perfusion pressure in guinea-pig isolated hearts perfused at constant flow. Blockers of other types of potassium channels, 4-aminopyridine and UK-66,914, did not significantly increase perfusion pressure. Exposing hearts to a single concentration of 3 microM glibenclamide caused a greater degree of vasoconstriction than when this was preceded by lower concentrations. The 3 microM glibenclamide-induced vasoconstriction was reduced by prazosin (1 microM), mepyramine (0.1 microM) and ranitidine (10 microM) but not by a combination of mepyramine and ranitidine or by ritanserin (0.01 microM). These results suggest that a component of the vasoconstriction induced by glibenclamide may result indirectly from the release of vasoactive mediators.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8105068&dopt=Abstract
Probl Endokrinol (Mosk). 1993 Sep-Oct;39(5):43-6.
[Status of ATP-dependent K+-channels of pancreatic beta-cells exposed to a series of sulfonylurea drugs]
[Article in Russian]
Babichev VN, Ignat'ev NS, Balabolkin MI.
The authors analyze the relationships between electrophysiologic processes taking place on beta-cell membranes under the effects of some second generation sulfonylurea drugs: gliclazide, glibenclamide, and glipizide and their secretogenic effects on insulin secretion. All the tested drugs induced complete blocking of K(+)-ATP-dependent channels when administered in concentrations from 1 to 20 microM (physiologic doses). Glucose had a similar effect. The canal is closed very soon, within 30 sec, and is closed for approximately 10 min, rapidly opening after the drug is washed away. Reduced activity of the channels up to their closure is conducive to the onset of insulin secretion. Glibenclamide proved to be the most potent suppressor of individual channel activity, this being confirmed by its more potent hypoglycemic effect as compared to gliclazide or glipizide.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8108350&dopt=Abstract
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