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Biomedical subjects

J R Azanza

Publications and source records attributed to J R Azanza.

At least 19 recordsLinked to original sources

[The most common infections in the transplanted patient].

Organ transplantation has become one of the most important areas of medical research and, at present, is still the only therapeutical tool for several diseases. However, there are a number of factors related to transplantation, like immunosuppression and prolonged neutropenia that affect the incidence of infection. These infections are somehow peculiar to transplant recipients. In fact, there are infectious diseases that only occur in immunodepression situations and, moreover, clinical expression of these infectious diseases can be quite different from that in immunocompetent patients. Besides these aspects, some infections, due to the high prevalence described, must be considered for prevention strategies because they continue to be a principal cause of morbidity and mortality, either due to direct effects or to their implication in the pathogenesis of rejection. These strategies commence before transplantation by active immunization through vaccine administration to the patient and to people in the milieu and continue after transplantation with prophylaxis or pre-emptive therapy. The importance of infectious diseases in the evolution and prognosis of transplant recipients gives a special meaning to the understanding of associated infections, their clinical expression and ways of prevention and treatment.

Heart Transplantation↗

Clinical relevance of sirolimus drug interactions in transplant patients.

Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. The CYP3A4/P-glycoprotein system is mainly localized in the liver and intestine. It is responsible for the severe first pass metabolism of sirolimus with a low bioavailability. Drugs like voriconazole, itraconazole, fluconazole, and erytrhomycin may decrease the metabolic activity of this enzymatic system. This report documents in five patients that coadministration of these antimicrobials with sirolimus increases the blood concentrations of the immunosuppressant. The dose-normalized trough blood concentration showed a mean increase of sevenfold with the coadministration of these drugs. It is essential to monitor the blood sirolimus concentrations and to adjust the sirolimus doses before and after coadministration of these drugs.

Aged↗

Relationship between pharmacokinetics and pharmacodynamics of beta-lactams and outcome.

The in-vitro susceptibility of an organism and the pharmacokinetics of an antimicrobial agent are two basic factors on which the choice of standardised treatment regimens is based. However, the inter-individual variability of these factors, which modifies the exposure of bacteria to an antibiotic in terms of time and quantity, is not usually taken into account. In 87 patients treated with beta-lactams (ceftriaxone, cefepime or piperacillin), the probability of failure was greater when the infectious process was located in tissues with barriers to the distribution of beta-lactams. Mean MICs of piperacillin and cefepime, but not ceftriaxone, were below the breakpoints in cases of both recovery and failure, but organisms isolated from patients with a poor outcome had higher MICs. Therefore, the use of breakpoints to determine the susceptibility of microorganisms was not satisfactory in predicting the outcome for a large number of patients. If MICs are determined and plasma concentrations are monitored, dosages can be adjusted according to these parameters, thereby allowing antibiotic treatment to be individualised.

Adult↗

Development of a chromatographic method for the determination of saquinavir in plasma samples of HIV patients.

A simple, sensitive and reproducible high-performance liquid chromatographic method for detecting and quantifying saquinavir in human plasma is described. Verapamil was used as internal standard. The method employes a single liquid-liquid extraction step with tert-butil methyl ether followed by chromatography on a Lichrospher 60 Select B C8 reversed-phase column. Ultraviolet detection was used to identify the compounds of interest. The quantitation limit of saquinavir was 1 ng/mL and only 0.5 mL of plasma sample was required for the determination. The average saquinavir recoveries over a concentration range of 2.5-500 ng/mL ranged from 86 to 95%. Precision and accuracy did not exceed 5%.

Calibration↗

Improved selectivity in detection of polar basic drugs by liquid chromatography-electrospray ionization mass spectrometry. Illustration using an assay method for the determination of famotidine in human plasma.

It is well to assume that bioanalytical chromatographic methods for the determination of polar basic drugs are developed and optimised according to a standardised procedure which involves two alternatives: (a) modifications in the sample preparation procedures, and (b) changes in the stationary phase of the chromatographic system. In this paper, a simple and rapid chromatographic procedure using a specific analytical detection method (ESI tandem mass spectrophotometric detection) in combination with a fast and efficient sample work-up procedure, protein precipitation, is presented. A demonstration of the entire chromatographic procedure is given for an HPLC method for the determination of famotidine in human plasma, a basic polar drug with poor solubility in organic solvents. In order to optimize the mass detection of famotidine, several parameters such as ionization mode, fragmentor voltage, m/z ratios of ions monitored, type of organic modifier and eluent additive, were investigated. Each analysis required 5 min. The calibration curve of famotidine in the range 1-200 ng/ml was linear with a correlation coefficient of 0.9992 (n = 6), and a detection limit a signal-to-noise ratio of 3 was approximately 0.2 ng/ml. The within- and between-day variations in the famotidine analysis were 5.2 (n = 6) and 6.7% (n = 18), respectively. The applicability of this method was also demonstrated for the analysis of plasma samples in a Phase-I human pharmacokinetic study.

Biological Availability↗

Rapid high-performance liquid chromatographic determination of cefepime in human plasma.

A simple, rapid and reproducible high-performance liquid chromatographic method for the quantitative determination of cefepime in human plasma was developed. Ceftazidime was used as internal standard. Chromatography was performed on a reversed-phase encapped column (Hypersil BDS C18). The samples, after protein precipitation, were eluted with a mobile phase of acetonitrile-acetate buffer, pH 4 (2.8:97.2, v/v). The detection wavelength was 254 nm. The limit of quantitation of cefepime was 0.5 microgram/mL and only 0.5 mL of plasma sample was required for the determination. The average cefepime recoveries over a concentration range of 0.5-500 micrograms/mL ranged from 98 to 104%. Precision and accuracy did not exceed 5%.

Cefepime↗

Development and validation of a sensitive method for the determination of ganciclovir in human plasma samples by reversed-phase high-performance liquid chromatography.

A rapid, sensitive, specific liquid chromatographic method has been developed for the determination of therapeutic levels of ganciclovir in human plasma. Plasma (1 ml) and acyclovir (I.S.) were treated with 50% trichloroacetic acid. The supernatant was neutralized with 2 M NaOH and purified with chloroform. The aqueous phase (80 microl) was analyzed by a 3-microm Hypersil ODS C18 column with 0.04 M triethylamine-0.1 M sodium dihydrogen phosphate monohydrate as the mobile phase (1 ml/min) and ultraviolet detection at 254 nm. Calibration was linear from 50 to 10000 ng/ml. Intra- and inter-day C.V. did no exceed 6.65%. The detection limit was about 10 ng/ml.

Antiviral Agents↗

Concurrent clarithromycin and cyclosporin A treatment.

Although macrolides have been associated with significant pharmacokinetic interactions, clarithromycin is considered to have a low interaction capacity. In this study, six transplant recipients treated with cyclosporin A also received clarithromycin. In all patients, the dose of cyclosporin A had to be reduced by a mean of 33% per day depending on the macrolide dose. Normalization of the dosage parameters began on the fourth day after stopping clarithromycin treatment. Co-administration of cyclosporin A and clarithromycin may lead to increases in whole blood cyclosporin levels, and appropriate dose reductions should be considered.

Anti-Bacterial Agents↗

Cimetidine does not alter sparfloxacin pharmacokinetics.

The interaction between cimetidine and sparfloxacin was studied in 10 healthy volunteers who received a single oral dose of 400 mg sparfloxacin on the third day of an 8 day cimetidine (400 mg t.i.d.) or placebo randomly assigned treatment. No statistically significant differences were observed in the pharmacokinetic parameters (Cmax-AUC-T1/2-urinary excretion and metabolic ratio) of sparfloxacin following the 2 treatment. Cimetidine does not affect absorption, metabolism or urinary excretion of sparfloxacin; consequently, patients exposed to this drug combination are not at risk.

Adult↗

Graft-versus-host disease after liver transplantation.

We describe a case of graft-versus-host disease that developed in the recipient of an orthotopic liver transplant. A maculopapular eruption developed on postoperative day 25. After the diagnosis of graft-versus-host disease was made aggressive therapy was instituted, which resulted in a complete recovery.

Exanthema↗