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Serum Drug Levels (serum + drug_level)
Selected AbstractsEffects and serum levels of glibenclamide and its active metabolites in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2001A. Jönsson SUMMARY Objective To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses. Material and methods Fifty patients with type 2 diabetes on regular Gb therapy (1.75,14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's R to Z -test (correlation coefficients) and paired Student t -tests were used when comparing values within the entire group and unpaired non-parametric Mann,Whitney tests were used when comparing high and low dose levels. A p-value <,0.05 was considered significant. Results There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAlc (r = 0.55), ,-insulin (r = , 0.59) and ,-proinsulin (r = , 0.52) levels. Significant correlations between Gb therapy duration and insulin (r = , 0.40) and proinsulin (r = , 0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r = 0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients on , 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0,120) and 33 (0,120) ng/ml) than those of Gb itself (18(0,64) ng/ml). A great inter-subject variability in Gb levels at both time points was seen. Conclusions Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired ,-cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down-regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events. [source] Increased risk of early virological failure in non-European HIV-1-infected patients in a Dutch cohort on highly active antiretroviral therapyHIV MEDICINE, Issue 5 2005JB Van Den Berg Objective To compare early and late responses to highly active antiretroviral therapy (HAART) in European and non-European HIV-1 infected patients in a Dutch cohort. Methods We retrospectively analysed the response to HAART of 216 previously treatment-naive HIV-1-infected patients using the University Medical Centre Utrecht HIV database. African (n=51), Asian (n=7), and Central/South American (n=6) patients were classified as non-European, and others as European (n=152). Early failure was defined as a viral load that remained above 400 HIV-1 RNA copies/mL after 6 months of treatment with HAART. Late-phase failure was determined in patients who were successfully treated in the early phase and was defined as two consecutive viral load measurements above 400 copies/mL, a new AIDS-defining event or death. Results In the early phase, four of 152 (2.6%) European and eight of 64 (12.5%) non-European patients failed HAART. A significant increased risk of virological failure in the early phase of treatment was observed for non-Europeans as compared to Europeans (odds ratio 4.6; 95% confidence interval 1.1,20.2). Low serum drug levels in the absence of resistant virus were often seen at the time of early failure. No difference in late-phase failure was observed between the two groups (adjusted hazard ratio 0.6; 95% confidence interval 0.3,1.2). Conclusions Non-European patients had a 4.6 times higher risk of virological failure than their European counterparts in the first 6 months of treatment with HAART. This failure seemed to be associated with low serum drug levels at the time of failure. However, if HAART was successful in the early phase, response rates in the late phase were similar for Europeans and non-Europeans. [source] Measurement of serum salicylate levels by solid-phase extraction and desorption/ionization on silicon mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2005Shoji Okuno Abstract The applicability of the matrix-free laser desorption/ionization on silicon mass spectrometry (DIOS-MS) to measuring serum drug levels was examined by analyzing serum salicylic acid. The optimized and simple solid-phase extraction (SPE) allowed good recovery, 88.9 ± 5.8%, for 1.4 mM (200 mg/L) of salicylic acid in serum. The negative ion MS allowed measurements of deprotonated molecules without interference from other signals. Using a deuterium-labeled internal standard, good linearity was obtained in the 0.14 to 4.2 mM (20,600 mg/L) range, which was sufficient for monitoring the therapeutic anti-inflammatory dose. SPE followed by DIOS-MS is anticipated to be a method of measuring drug levels in blood and may allow high throughput analysis. Copyright © 2005 John Wiley & Sons, Ltd. [source] Hydrogenated castor oil nanoparticles as carriers for the subcutaneous administration of tilmicosin: in vitro and in vivo studiesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009C. HAN Tilmicosin-loaded solid lipid nanoparticles (SLN) were prepared with hydrogenated castor oil (HCO) by o/w emulsion,solvent evaporation technique. The nanoparticle diameters, surface charges, drug loadings and encapsulation efficiencies of different formulations were 90,230 nm, ,6.5,,12.5 mV, 40.3,59.2% and 5.7,11.7% (w/w), respectively. In vitro release studies of the tilmicosin-loaded nanoparticles showed a sustained release and the released tilmicosin had the same antibacterial activity as that of the free drug. Pharmacokinetics study after subcutaneous administration to Balb/c mice demonstrated that a single dose of tilmicosin-loaded nanoparticles resulted in sustained serum drug levels (>0.1 ,g/mL) for 8 days, as compared with only 5 h for the same amount of tilmicosin phosphate solution. The time to maximum concentration (Tmax), half-life of absorption (T½ ab) and half-life of elimination (T½ el) of tilmicosin-loaded nanoparticles were much longer than those of tilmicosin phosphate solution. Tissue section showed that drug-loaded nanoparticles caused no inflammation at the injection site. Cytotoxicity study in cell culture and acute toxicity test in mice demonstrated that the nanoparticles had little or no toxicity. The results of this exploratory study suggest that the HCO,SLN could be a useful system for the delivery of tilmicosin by subcutaneous administration. [source] | ||||||||||