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J Pharmacobiodyn. 1992 Mar;15(3):91-7.
Selective analysis of mutual displacement effects at the primary binding sites of phenoxymethylpenicillin and cephalothin bindings to human serum albumin.

Terasaki T, Nouda H, Tsuji A.

Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.

In order to analyze the mutual displacement effects on the protein binding of beta-lactam antibiotics, binding experiments with the human serum albumin (HSA) were performed for cephalothin (CET) and phenoxymethylpenicillin (PCV) by using the centrifugal ultrafiltration method. The numbers of primary and secondary binding sites, n1 and n2, and the affinity constants for the primary and secondary binding sites, K1 and K2 were determined for CET to be 1.00 +/- 0.06 (mean +/- S.D.) and 4.54 +/- 0.12 and 2.59 x 10(3) +/- 0.10 x 10(3) (M-1) and 2.59 x 10(2) +/- 0.16 x 10(2) (M-1), respectively, and for PCV to be 0.94 +/- 0.10 and 5.41 +/- 0.40 and 3.52 x 10(3) +/- 0.25 x 10(3) (M-1) and 4.07 x 10(2) +/- 0.54 x 10(2) (M-1), respectively. Using the predicted optimum unbound concentration of PCV, i.e., 4.6 x 10(-4) M, the displacement effect of PCV to the binding of CET at the primary site has been demonstrated, while no significant effect was observed at the secondary binding site. Moreover, a competitive displacement effect of CET was also demonstrated for the binding of PCV to HSA at the primary binding site, suggesting that CET and PCV bound to HSA at the same primary binding site.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1625169&dopt=Abstract




Acta Otolaryngol Suppl. 1992;492:68-71.
Penicillin tolerance in group A streptococci and treatment failure in streptococcal tonsillitis.

Stjernquist-Desatnik A, Orrling A, Schalen C, Kamme C.

Department of Otorhinolaryngology, University of Lund, Sweden.

Penicillin tolerance in Streptococcus pyogenes has been suggested as a possible cause of therapeutic failure in streptococcal phryngitis treated with penicillin. In 144 patients with acute group A streptococcal tonsillitis treated with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days the same T-type was recovered after treatment in 21%. The recovery rate was higher for non-tolerant strains, 23%, than for tolerant strains, 10% (p greater than 0.05). Of patients with a non-tolerant strain 17% had both clinical and bacterial treatment failure in comparison with 5% infected with a tolerant strain (p greater than 0.05). Reinfection with a new serotype occurred in altogether 3%. The present data did not indicate that penicillin tolerance in group A streptococci is of significance in acute tonsillitis treated with phenoxymethylpenicillin for 10 days.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632256&dopt=Abstract




J Chromatogr. 1992 Feb 28;593(1-2):15-20.
High-performance liquid chromatographic determination of penicillin G, penicillin V and cloxacillin in beef and pork tissues.

Moats WA.

US Department of Agriculture, Product Quality and Development Institute, Beltsville, MD 20705-2350.

The objective was to develop confirmatory high-performance liquid chromatographic methods for penicillin residues in animal tissues with detection limits of less than or equal to 10 ng/g. A previously described procedure was modified by using a larger sample size and isocratic analysis. Tissues (15 g) were blended with 45 ml of water and 20 ml of homogenate were mixed with 40 ml acetonitrile and filtered. The filtrate (30 ml) was mixed with 10 ml of 0.2 M H3PO4 and extracted with methylene chloride. The combined methylene chloride layers were mixed with acetonitrile and hexane, washed with two 4-ml portions of water and then extracted with four 1-ml portions of 0.01 M phosphate buffer (pH 7). The combined buffer extracts were concentrated to 1 ml under reduced pressure. Analysis was isocratic during 0.01 M phosphate buffer (pH 7)-acetonitrile with proportions 85:15 (penicillin G), 82:18 (penicillin V) or 78:22 (cloxacillin). A polystyrene-divinylbenzene copolymer column, 150 x 4.6 mm I.D. (Polymer Labs. PLRP-S), was used with a flow-rate of 1 ml/min and detection at 210 nm. The presence of penicillins was confirmed by treating a duplicate sample with penicillinase. Recoveries were greater than 90% in most instances. Detection limits were 5 ng/g in muscle and higher in liver and kidney. The procedure is a simple and sensitive method for confirming the presence of penicillins in animal tissues.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1639899&dopt=Abstract













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