Drugs online research references
J Neurochem. 2002 Oct;83(1):57-66.
Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain.
Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T.
Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Renal impairment is associated with CNS dysfunctions and the accumulation of uremic toxins, such as indoxyl sulfate, in blood. To evaluate the relevance of indoxyl sulfate to CNS dysfunctions, we investigated the brain-to-blood transport of indoxyl sulfate at the blood-brain barrier (BBB) using the Brain Efflux Index method. [(3)H]Indoxyl sulfate undergoes efflux transport with an efflux transport rate of 1.08 x 10(-2)/min, and the process is saturable with a Km of 298 microm. This process is inhibited by para-aminohippuric acid, probenecid, benzylpenicillin, cimetidine and uremic toxinins, such as hippuric acid and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid. RT-PCR revealed that an OAT3 mRNA is expressed in conditionally immortalized rat brain capillary endothelial cell lines and rat brain capillary fraction. Xenopus oocytes expressing OAT3 were found to exhibit [(3)H]indoxyl sulfate uptake, which was significantly inhibited by neurotransmitter metabolites, such as homovanillic acid and 3-methoxy-4-hydroxymandelic acid, and by acyclovir, cefazolin, baclofen, 6-mercaptopurine, benzoic acid, and ketoprofen. These results suggest that OAT3 mediates the brain-to-blood transport of indoxyl sulfate, and is also involved in the efflux transport of neurotransmitter metabolites and drugs. Therefore, inhibition of the brain-to-blood transport involving OAT3 would occur in uremia and lead to the accumulation of neurotransmitter metabolites and drugs in the brain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12358729&dopt=Abstract
ribapharm.com
Ribavirin is a purine nucleoside analog with broad spectrum activity against a spectrum of DNA and RNA viruses. To facilitate pharmacokinetics studies, a LC-MS-MS method for the analysis of ribavirin in rat and monkey plasma was developed and validated. The method involved the addition of acyclovir as an internal standard and protein precipitation with acetonitrile followed by separation by an Intertsil Silica column and quantification by a MS-MS equipped with a positive electrospray ionization in the multiple reaction monitoring mode. The MS-MS reaction was selected to monitor the 245-->113 and 226-->152 transitions for ribavirin and internal standard, respectively. The calibration curve was linear over a concentration range of 10-5000 ng/ml. The lower limit of quantitation was 10 ng/ml, the coefficient of variation (CV) was 8-11%, and the bias was 1-3%. Intra-day and inter-day analysis of QC samples at 30, 1500 and 3500 ng/ml indicate that the method was precise (CV<18%) and accurate (bias<13%). Ribavirin in rat and monkey plasma was stable at 5 degrees C for at least 24 h, 0 degrees C for at least 4 h, and after three freeze-thaw cycles. This specific, accurate and precise assay is useful in the study of the pharmacokinetics of this compound.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12361738&dopt=Abstract
J Chromatogr B Biomed Sci Appl. 1997 Mar 7;690(1-2):363-6.
Determination of acyclovir and its metabolite 9-carboxymethoxymethylguanine in serum and urine using solid-phase extraction and high-performance liquid chromatography.
Svensson JO, Barkholt L, Sawe J.
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
A reversed-phase ion-pair high-performance liquid chromatography method for the determination of acyclovir and its metabolite 9-carboxymethoxymethylguanine is described. The sample are purified by reversed-phase solid-phase extraction. The components are separated on a C18 column with a mobile phase containing 18% acetonitrile, 5 mM dodecyl sulphate and 30 mM phosphate buffer, pH 2.1, and measured by fluorescence detection using an excitation wavelength of 285 nm and an emission wavelength of 380 nm. Detection limits are 0.12 microM (plasma) and 0.60 microM (urine) for acyclovir, and 0.26 microM (plasma) and 1.3 microM (urine) for metabolite. Correlation coefficients that were better than 0.998 were obtained normally. This analytical method, which enables simultaneous measurement of parent compound and metabolite, has been used in kinetics studies and for therapeutic drug monitoring in different patient groups with variable degrees of renal dysfunction.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9106067&dopt=Abstract
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