Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of hypertension in haemodialyzed uraemic patients is multifactorial. The following are involved: sodium and water retention as a result of the impaired excretory capacity of the kidneys, excessively increased activity of the RAAS and sympathetic nerve, increased levels of the vascular constrictor endothelin-1, cumulation of endogenous inhibitors of NO synthesis and reduced formation of vasodepressor factors. As to other factors in the development of hypertension raised intracellular calcium associated with hyperparathyroidism may participate, the stiffness of calcified arteries, erythropoietin treatment and preexisting essential hypertension. Treatment comprises salt restriction below 5 g/day, systematic control of the volume of extracellular fluid by ultrafiltration during every haemodialysis to the level of so-called dry weight and pharmacological treatment in patients where volume control dos not suffice. All drug groups are used. In their selection contraindications are taken into consideration as well as co-morbidity, the dialyzability of antihypertensive drugs and compelling evidence. In patients with a preserved residual diuresis furosemide is administered--125-750 mg/day. Beta-blockers are indicated in patients with IHD, in particular after IM. Calcium blockers are recommended in ventricular hypertrophy and diastolic dysfunction, when beta-blockers are contraindicated and in elderly patients. ACEI indicated in congestive heart failure and left ventricular hypertrophy with systolic dysfunction. Inhibitors of AT1 receptors are an alternative in case of undesirable effects od ACEI. Alpha-blockers and central alpha agonists are used mainly in combinations. In case of failure the haemodialyzation method can be altered or changing the patients to CAPD may be considered. The relationship between BP and the survival of haemodialyzed patients is bimodal. An adverse effect is exerted by a high as well as low BP and in particular by interdialyzation hypotension. The target BP for the haemodialyzed population has not been defined so far. There is, however, evidence that a high BP is independently associated with the de novo development of IHD and MAP above 106 mm Hg with de novo development of cardiac failure. MAP below 98 mm Hg minimalizes the development and progression of left ventricular hypertrophy and MAP below 106 mm Hg the development of heart failure. Long-term survival for 15 and more years is statistically significantly associated with MAP lower than 99 mm Hg.
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PMID:[Hypertension in hemodialyzed uremic patients]. 1095 54

High-performance liquid chromatography separation of reduced and oxidized glutathione (GSH and GSSG) in biologic samples using electrochemical detection offers the convenience of both simultaneous quantitation and simple sample preparation. Rapid acidification is required to prevent GSH autooxidation, GSH and GSSG degradation, and precipitate proteins that interfere with analysis. Currently, little consistency exists in the literature regarding acid selection or the feasibility of sample storage before analysis. The purpose of this work was to examine the effects of perchloric (PCA), trichloroacetic (TCA), metaphosphoric (MPA), and 5-sulfosalicylic (SSA) acids on the short-term stability of GSH and GSSG measurements in whole blood. Samples were collected from adult volunteers and treated with multiple concentrations of each acid. The samples were analyzed immediately and aliquots were stored at -80 degrees C for up to 28 days. The suitability of each acid was assessed by percentage change of GSH and GSSG from baseline, efficiency of protein removal, and alteration of chromatogram characteristics. In general, increasing the acid concentration improved sample stability. Nevertheless, SSA did not achieve acceptable sample stability at any concentration tested. MPA was found to leave substantial amounts of protein in the samples, and TCA may interfere with the peaks of interest. Based on these results, a final concentration of 15% PCA is suggested for analysis of glutathione in whole blood. Although immediate sample preparation is preferred, 15% PCA can maintain sample integrity for 4 weeks after storage at -80 degrees C.
Ther Drug Monit 2001 Oct
PMID:Glutathione stability in whole blood: effects of various deproteinizing acids. 1159 1

High-dose ibuprofen therapy has demonstrated to slow deterioration in pulmonary function in children with cystic fibrosis with mild lung disease. Therapeutic drug monitoring has been recommended to maintain peak concentrations within the range of 50 to 100 mg/L to ensure efficacy. Current methods for dosage individualization are based on dose proportionality using visual inspection of the peak concentration; however, because of interpatient variability in the absorption of the various formulations this method may result in incorrect assessments of the peak concentration achieved. Maximum a posteriori Bayesian analysis (MAP-B) has proven to be a useful and precise method of individualizing the dose of aminoglycosides but requires a description of the structural model. In this study we performed parametric population modeling analysis on plasma concentrations of ibuprofen after single doses of 20 to 30-mg/kg tablet or suspension in children with cystic fibrosis. Patients evaluated in this study were part of a single dose pharmacokinetic study that has been published previously. A one-compartment model with first order absorption and a lag time best described the data. The pharmacokinetic parameters differed significantly depending on the formulation administered. D-optimal sampling times for the suspension and tablet formulations are 0, 0.25 to 0.5, 1, and 3 to 4 hours and 0, 0.25 to 0.5, 1 to 1.5, and 5 hours respectively. Use of MAP-B analysis performed with the 4 d-optimal sampling strategy resulted in accurate and precise estimates of the pharmacokinetic parameters when compared with maximum likelihood analysis using the complete plasma concentrations data set. Further studies are needed to evaluate the performance of these models and the impact on patient outcomes.
Ther Drug Monit 2002 Apr
PMID:Development of population pharmacokinetic models and optimal sampling times for ibuprofen tablet and suspension formulations in children with cystic fibrosis. 1189 78

This paper evaluates the performance of the NIOSH draft method 5525 for analysis of monomeric and TRIG aliphatic isocyanates in autobody repair shops. It was found that an optimized pH gradient enhanced noticeably the resolution and, therefore, identification of aliphatic isocyanates. Samples proved to be very stable for at least a year when stored at -13 degrees C in the freezer, and no major stability problems were found for the MAP reagent. The detector response factor RSD for selected MAP ureas was 40% in the fluorescence (FLD), 3% in the UV at 254 nm (UV254), and 1% in the UV at 370 nm (UV370). The mean FLD/UV254 and UV254/UV370 detector response ratios of standards were 31.7 (RSD = 37.8) and 17.1 (RSD = 5.4), respectively. The FLD/UV254 ratio in bulks varied from 0.41 to 1.97 times the HDI monomer ratio. The mean UV254/UV370 ratio in bulks was 16.1 (range 14.1 to 19.2, N = 38). Mean (range) recovery of 92 (91.2-93.2)% was found for the N3300 (isocyanurate) spiked on 25 mm quartz fiber filters in the range 0.07 to 2.2 microg NCO ml(-1). Mean (range) recovery for impingers was 100.7 (91.7-106.0)% for N3300 in the concentration range of 0.018 to 2.5 microg NCO ml(-1) and 81.0 (76.1-89.1)% for IPDI in the concentration range of 0.016 to 1.87 microg NCO ml(-1). Analytical method precision was 3.4% and mean bias 7.4% (range = 0-25%). The NIOSH draft method 5525 provides flexibility, enhanced sensitivity and specificity, powerful resolution, and very small compound-to-compound variability in the UV254, resulting in a more reliable identification and quantification of aliphatic isocyanates.
J Environ Monit 2002 Jun
PMID:Evaluation of the NIOSH draft method 5525 for determination of the total reactive isocyanate group (TRIG) for aliphatic isocyanates in autobody repair shops. National Institute for Occupational Safety and Health. 1209 28

The aims of the current study were (1) to study Neoral pharmacokinetics (PK) in stable lung recipients with or without cystic fibrosis (CF), (2) to compare Neoral PK between these two groups, and (3) to design Bayesian estimators for PK forecasting and dose adjustment in these patients using a limited number of blood samples. The individual PK of 19 adult lung transplant recipients, 9 subjects with CF and 10 subjects without CF, were retrospectively studied. Three profiles obtained within 5 days were available for each patient. A PK model combining a gamma distribution to describe the absorption profile and a two-compartment model were applied. Different exposure indices were estimated using nonlinear regression and Bayesian estimation. The PK model developed reliably described the individual PK of Neoral in lung transplant patients with and without CF, and the values of the first and second half-lives were different in these two populations (lambda(1) = 4.14 +/- 3.01 vs. 2.16 +/- 1.75 h(-1); P < 0.01; lambda(2) = 0.36 +/- 0.11 vs. 0.49 +/- 0.12 h(-1); P < 0.01), while the mean absorption time and standard deviation of absorption time tended to be less in patients with cystic fibrosis (P < 0.1). Also, the patients with CF required higher doses than those without CF to achieve similar drug exposure. Consequently, population modeling was performed in CF and non-CF patients separately. Bayesian estimation allowed accurate prediction of AUC(0-12), AUC(0-4), C(max), and T(max) using three blood samples collected at T0h, T1h, and T3h in both groups. This study demonstrated the applicability and good performance of the PK model previously developed for oral cyclosporin and of the MAP Bayesian estimation of cyclosporin systemic exposure in CF and non-CF patients. Moreover, it is the first to propose a monitoring tool specifically designed for cyclosporin monitoring in patients with CF.
Ther Drug Monit 2003 Feb
PMID:Bayesian forecasting of oral cyclosporin pharmacokinetics in stable lung transplant recipients with and without cystic fibrosis. 1254 41

Getting the most effective use of immunosuppressant medications in transplant patients continues to be a major challenge in clinical practice. This need applies to established immunosuppressants just as it does to new agents. In this review this principle is illustrated for mycophenolic acid, the active metabolite of mycophenolate mofetil, the most commonly used immunosuppressant, in various combinations with other immunosuppressants, in current clinical practice. Defining, as rigorously as possible, the requirements for effective therapeutic monitoring of MPA is an important goal given all of the changes in immunosuppressive drug regimens. This review will focus on the major factors known to influence MPA clearance including: UDP-glucuronyltransferases, enterohepatic circulation, MPA free fraction, the effect of time posttransplantation, concomitant administration of immunosuppressant drugs. The significant variability of MPA pharmacokinetics and the need to deepen our understanding of the influence of these factors on MPA clearance are strong reasons why additional clinical trials are needed to define best practice therapeutic drug monitoring of this drug.
Ther Drug Monit 2004 Aug
PMID:Using established immunosuppressant therapy effectively: lessons from the measurement of mycophenolic acid plasma concentrations. 1525 62

After a brief overview of the relevant exposure indices for cyclosporine (CsA) and mycophenolate mofetil (MMF), as well as of the different steps necessary to develop maximum a posteriori Bayesian estimators (MAP-BE), this paper presents applications of MAP-BE for CsA or MMF to clinical cases and clinical trials. Ina renal transplant patient under CsA, grade I chronic allograft nephropathy was found at the sixth month posttransplantation, with CsA CO slightly above the target range and C2 markedly below; the AUCO0-12 h Bayesian estimate was quite high, at 5.6 mg h/L, as compared with a mean value of 4.3+0.9 mg.h/L in stable renal transplants at this period; the inconsistent C2 level found could be explained by delayed absorption of CsA in this patient, in which case C2 no longer represents the major part of the AUC. The patient was switched to sirolimus, which resulted in a slow and significant improvement of graft function with no acute rejection. In a 50-year-old female renal transplant recipient administered MMF and CsA and with a very favorable outcome otherwise, progressive anemia appeared 8 months posttransplantation. Clinical investigations were negative,but Bayesian estimation showed a rather high MPA AUCO0-12 h (69.8 mg h/L). After MMF dose reduction, hemoglobin level progressively returned to normal, without erythropoietin injection or blood transfusion. Finally, the feasibility of accurate dose adjustment using these MAP-BE is shown through preliminary results from 2 ongoing multicenter clinical trials, 1 evaluating an AUC-controlled cyclosporine-sparing strategy in stable renal transplants, the second evaluating the benefit of MMF therapeutic drug monitoring based on MPA AUCO0-12 h in de novo renal transplant recipients.
Ther Drug Monit 2005 Dec
PMID:Clinical application of population pharmacokinetic methods developed for immunosuppressive drugs. 1640 5

The most prominent theory describes the Crohn's Syndrome as a dysregulated, inappropriate immune response to otherwise innocuous bowel flora in a genetically susceptible host. The autoimmune theory assumes that a specific infectious agent does not exist. Data from mouse models, impairment of the mucosal epithelial barrier and the influence of gut flora are used to support the autoimmune theory. Critics claim that the dysregulated immune responses are not the primary disorder but secondary to an underlying infection. Two other theories are also consistent with the same data. The immunodeficiency theory hypothesizes that defects in innate immunity leading to compensatory immune processes underlie the Crohn's phenotype and suggests that therapy should stimulate immunity rather than suppress it. The mycobacterial theory proposes that Mycobacterium avium subspecies paratuberculosis is one of the causes of the Crohn's Disease syndrome. Mycobacterial molecules dysregulate immune signaling pathways as part of the organisms'evolved survival strategy. If MAP were to initiate the dysregulated immune response then the necessity to hypothesize that commensal gut flora provide the antigenic stimulus would be moot. Commensal bacteria would be relegated to a secondary role of modifying the immune response rather than occupying the central role of providing the initiating antigens. Critics claim that MAP is merely a secondary invader. The three theories differ primarily by emphasizing different aspects of the same overall process.
Med Sci Monit 2006 Feb
PMID:Integrating theories of the etiology of Crohn's disease. On the etiology of Crohn's disease: questioning the hypotheses. 1664 83

A roundtable meeting to discuss the use of therapeutic drug monitoring (TDM) to guide immunosuppression with mycophenolate mofetil was held in New York in December 2004. Existing recommendations for the initial months after transplantation were updated. After ensuring adequate levels of mycophenolic acid (MPA, the active metabolite of mycophenolate mofetil) immediately after transplantation, optimal efficacy may require only a few dose adjustments, because intrapatient variability in exposure seems low. Recommendations based on current knowledge were made for posttransplantation sampling time points and for target MPA concentrations. Algorithms for estimating MPA exposure using limited sampling strategies were presented, and a new assay for MPA discussed. It was agreed that because of interpatient variability and the influence of concomitant immunosuppressants, TDM might help optimize outcomes, especially in patients at higher risk of rejection. The value of TDM in the general transplant population will be assessed from large, ongoing, randomized studies.
Ther Drug Monit 2006 Apr
PMID:Therapeutic drug monitoring of mycophenolate mofetil in transplantation. 1662 23

We have developed a new fully automated method for mycophenolic (MPA) acid quantification in plasma to optimize therapeutic drug monitoring of tranplant patients. This method involved solid-phase extraction on disposable extraction cartridges and reversed-phase high-performance liquid chromatography with diode array detection. Solid-phase extraction was performed automatically by an automated sample with extraction catridges system. After washing, MPA was eluted from the cartridge onto a Chromolith RP-18e column. MPA and the internal standard were detected at 306 nm. The retention time of MPA was 6.3 minutes. The developed method was linear from 0.2 to 20 microg/mL. The limit of quantification was 0.2 microg/mL. The method showed a good precision with intraday and interday variation coefficient less than 6%. The intraday accuracy ranged from 97.6% to 100.4% and the interday accuracy varied from 97.1% to 100.8%. The extraction efficiency was greater than 90%. This method is simple and shows a good specificity with respect to commonly co-prescripted drugs.
Ther Drug Monit 2006 Aug
PMID:Fully automated analytical method for mycophenolic acid quantification in human plasma using on-line solid phase extraction and high performance liquid chromatography with diode array detection. 1688 17


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