Drugs online research references
J Laryngol Otol. 1993 Apr;107(4):309-12.
Penetration of penicillin V to tonsillar surface fluid in healthy individuals and in patients with acute tonsillitis.
Stjernquist-Desatnik A, Samuelsson P, Walder M.
Department of Oto-Rhino-laryngology, University Hospital, Lund, Sweden.
In the treatment of group A streptococcal tonsillitis, as the bacteria are located on the epithelial surface, an important determinant of outcome is the concentration of penicillin in extracellular tonsillar surface fluid. Accordingly, we investigated the concentration of penicillin in serum, and penetration to tonsillar surface fluid and saliva in nine patients with acute group A streptococcal tonsillitis and in nine healthy controls. Among the healthy subjects, despite high serum penicillin concentrations (mean, 2.04 micrograms/ml), there was no penetration to tonsillar surface fluid or to saliva, whereas erythromycin penetrated to tonsillar surface fluid in 3/6 cases. Of the nine patients with acute tonsillitis, on the first day of treatment eight manifested high concentrations of penicillin in tonsillar surface fluid (mean, 0.34 micrograms/ml--i.e. well above the minimal inhibitory concentration (MIC) for group A streptococci), but penetration to saliva was found in only two patients. On the tenth day of treatment, penicillin was not present in the saliva of any of the patients and was present in the tonsillar surface fluid of only one. The results suggest that measurable concentrations of penicillin in tonsillar surface fluid can only be obtained in the presence of inflammation with fluid exudation through the tonsillar epithelium.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8320515&dopt=Abstract
J Pharm Sci. 1993 Jan;82(1):48-51.
Comparison of the in vivo and in vitro nuclear magnetic resonance detection of trifluoromethyl penicillin V in rats.
Campbell GD, Ramaprasad S, Olsen KM, Tryka AF, Komoroski RA, Blaszczak LC, Parr TR Jr.
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Fluorine nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging were examined as noninvasive methods for characterizing antibiotic disposition and pharmacokinetics in vivo. For determination of their utility, a 19F surface coil was constructed and an m-(trifluoromethyl)-containing penicillin V analogue (LY242072; 1) was synthesized. Various concentrations of 1 were injected intravenously into anesthetized rats whose urethras were occluded. The animals were placed on the surface coil, which was tuned to 19F, and then into a 4.7-T, 33-cm bore instrument, in which in vivo measurements of 1 were made on urine excreted into the bladder. At sacrifice, the urine was collected, and antibiotic levels were determined in vitro by both HPLC and high-resolution NMR. The limit of detection of 1 by NMR was 0.7 mg/mL of urine. When compared with standard in vitro quantitative methods using current technology, quantitation by in vivo surface coil NMR is not precise. Magnetic resonance imaging was used to image the bladder at a 35-mm3 voxel resolution with datum collection times of approximately 1 h. The 19F surface coil was used successfully to spectroscopically locate xenobiotic fluorine in the rat thorax. 19F NMR may offer an opportunity for the noninvasive in vivo detection of the distribution of various classes of therapeutic compounds.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8429491&dopt=Abstract
Bioconjug Chem. 1993 Jan-Feb;4(1):54-62.
Copolymers of lysine and polyethylene glycol: a new family of functionalized drug carriers.
Nathan A, Zalipsky S, Ertel SI, Agathos SN, Yarmush ML, Kohn J.
Department of Chemistry, Rutgers-State University of New Jersey, New Brunswick 08903.
Poly(PEG-Lys), a new, water-soluble poly(ether urethane), derived from L-lysine and poly(ethylene glycol) was investigated as a precursor for the preparation of polymeric drug conjugates. To facilitate a wide variety of coupling chemistries, the pendent carboxyl groups of poly(PEG-Lys) were converted to other reactive functional groups (amino, hydroxyl, active ester, and aldehyde) in high yield. These reactive pendent chains were then used as anchors for the covalent attachment of penicillin V and cephradine, two clinically used antimicrobial agents. Coupling to the carrier was achieved in good yields and the chemical versatility of this system was demonstrated by the preparation of conjugates having antibiotic ligands linked via biostable or biodegradable linkages to the carrier, either directly or via a spacer. Conjugate 4, poly(PEG-Lys-penicillin V ester), was obtained by linking penicillin V to the polymer backbone via hydrolytically labile ester bonds. This conjugate exhibited activity similar to that of the parent drug against three clinically important strains of bacteria. Drug activity coincided with the release of the drug from the carrier. Hydrolytically stable cephradine-containing conjugates were prepared by three different coupling methods but showed no antibiotic activity. 14C-labeled poly(PEG-Lys) was injected into mice and its biodistribution was monitored for 48 h. The carrier showed no preferential uptake by liver, spleen, or kidney. No signs of acute toxicity were evident in mice or rats when poly(PEG-Lys) was administered iv and ip at doses up to 10 g/kg. These results indicate that poly(PEG-Lys) is a promising precursor for the preparation of soluble drug conjugates.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8431513&dopt=Abstract
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