Nuestros investigadores

Azucena Aldaz Pastor

Clínica Universidad de Navarra. Clínica Universidad de Navarra
Farmacia y Tecnología Farmaceútica
Facultad de Farmacia y Nutrición. Universidad de Navarra
Índice H
11, (WoS, 23/01/2017)

Publicaciones científicas más recientes (desde 2010)

Autores: Chaccour Diaz, Carlos Javier; Hammann, F., ; Alustiza, M., ; et al.
ISSN 2045-2322  Vol. 7  Nº 1  2017  págs. 8535
Mass administration of endectocides, drugs that kill blood-feeding arthropods, has been proposed as a complementary strategy to reduce malaria transmission. Ivermectin is one of the leading candidates given its excellent safety profile. Here we provide proof that the effect of ivermectin can be boosted at two different levels by drugs inhibiting the cytochrome or ABC transporter in the mammal host and the target mosquitoes. Using a mini-pig model, we show that drug-mediated cytochrome P450/ABC transporter inhibition results in a 3-fold increase in the time ivermectin remains above mosquito-killing concentrations. In contrast, P450/ABC transporter induction with rifampicin markedly impaired ivermectin absorption. The same ketoconazole-mediated cytochrome/ABC transporter inhibition also occurs outside the mammal host and enhances the mortality of Anopheles gambiae. This was proven by using the samples from the mini-pig experiments to conduct an ex-vivo synergistic bioassay by membrane-feeding Anopheles mosquitoes. Inhibiting the same cytochrome/xenobiotic pump complex in two different organisms to simultaneously boost the pharmacokinetic and pharmacodynamic activity of a drug is a novel concept that could be applied to other systems. Although the lack of a dose-response effect in the synergistic bioassay warrants further exploration, our study may have broad implications for the control of parasitic and vector-borne diseases.
Autores: Milara, J., ; Outeda-Macias, M., ; Aumente-Rubio, M. D., ; et al.
ISSN 1130-6343  Vol. 39  Nº 1  2015  págs. 29 - 43
Objective: Dual PEGylated interferon-¿ (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Methods: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. Results: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNF¿ (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. Conclusions: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.
Autores: Martín Romano, Patricia; Aldaz Pastor, Azucena; Chopitea Ortega, Ana; et al.
ISSN 1969-2420  Vol. 32  Nº 3  2014  págs. S356
Autores: Rodríguez Rodríguez, Javier; Martín Romano, Patricia; Aldaz Pastor, Azucena; et al.
ISSN 0732-183X  Vol. 32  Nº Supl. 3  2014  págs. 579
Autores: Llombart Blanco, Rafael; Alfonso Olmos-García, Matías; Villas Tomé, Carlos; et al.
ISSN 0940-6719  Vol. 23  Nº 1  2014  págs. 276 - 277
Autores: Fusco, Juan Pablo; Martín Romano, Patricia; Aldaz Pastor, Azucena; et al.
ISSN 0923-7534  Vol. 25  Nº 2  2014  págs. 83 - 84
Introduction: Preoperative chemotherapy remains an experimental approach in patients (pts) with locally advanced colon cancer (LACC) that is being actively tested in ongoing randomised trials. We assessed the feasibility and preliminary evidence of activity of incorporating a direct monitoring of 5-FU levels based on pharmacokinetic-(PK) guided dose adjustments. Methods: Radiologically-staged LACC pts (T4 or T3 with >5mm invasion beyond the muscularis propia), were planned to receive 4 cycles of Oxaliplatin (85mg/m2), Leucovorin (400 mg/m2), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m2 in 46h and subsequent cycles tailored according to PK monitoring in order to reach a target 5-FU area under the curve (AUC) between 20-30 mg·h·L-1) on a biweekly basis. Surgery was scheduled 4 to 6 weeks after the completion of chemotherapy treatment. All pts were staged at baseline and before surgery. Pathological tumor regression was graded according to the MSKCC classification. Toxicity was reported according to the NCI-CTCAE 4.0. Results: From March 2011 to August 2013, 19 pts (M/F: 13/6; median age 60) with LACC were evaluated. Median dose of 5-FU was 5000 mg. 78.9% of the pts required a 5-FU dose increase to reach the target AUC. Median 5-FU plasma clearance was 199,58 L/h. Side effects profile included G3 neutropenia (6 pts), G2 diarrhea (5 pts), G2 nausea (3 pts) and G2 asthenia (5 pts). Neoadjuvant treatment was discontinued in 2 pts due to small bowel obstruction requiring surgery. No progressive disease was observed during preoperative chemotherapy. A radiological dowstaging was achieved in 11 pts (58%). All pts underwent surgery (laparoscopy-assisted 50%) with an R0 resection rate of 89.47%. There were no treatment-related deaths. Pathological responses (MSKCC score) included grades 4, 3+ and 3 in 10.5%, 15.78% and 21% of pts, respectively. Median number of harvested nodes was 23 (7-51) with a ypN0 rate of 79%. Median time to hospital discharge was 9 days. After a median follow-up of 15 months (6-35), the 12-month actuarial PFS and OS were 76.5% and 97.4%, respectively. Conclusion: Preoperative PK-adjusted FOLFOX in LACC pts is safe and well tolerated, achieving major pathological responses in almost 50% the pts and a remarkable R0 resection rate. This strategy may be an alternative in the management of patients with LACC but further research seems warranted. Almost 80% of the patients required a dose increase to achieve target dose levels.
Autores: Landecho Acha, Manuel Fortún; Alegre Garrido, Félix; Lucena Ramírez, Juan Felipe; et al.
ISSN 0887-8994  Vol. 51  Nº 3  2014  págs. e9-e10
Currently there is no strong evidence to recommend any determined trough plasma levels, and thus we wait for additional observations and clinical trials to clarify the optimal dosage required to avoid unnecessary side effects. Meanwhile, we have found a safe and acceptable response with plasma levels within the lower range of efficacy described.
Autores: Landecho Acha, Manuel Fortún; Alegre Garrido, Félix; Lucena Ramírez, Juan Felipe; et al.
ISSN 0887-8994  Vol. 51   Nº 3  2014  págs. e9 - e10
Autores: Aldaz Pastor, Azucena; Ferriols, R.; Aumente, D.; et al.
ISSN 1130-6343  Vol. 35  Nº 6  2011  págs. 326 - 339
Monitoring plasma levels of antiepileptic drugs for the treatment and prophylaxis of epilepsy is one of the strategies enabling clinical results to improve by reducing adverse affects and increasing effectiveness. The objective of this article is to review the basic aspects in the monitoring of antiepileptic drugs using a consensus document prepared and endorsed by the pharmacokinetics and pharmacogenetics working group (PK.gen) of the Sociedad Española de Farmacia Hospitalaria
Autores: Aldaz Pastor, Azucena
ISSN 1130-6343  Vol. 35  Nº 4  2011  págs. 163 - 164
Autores: Alfonso Olmos-García, Matías; Silva González, Álvaro Antonio; Aldaz Pastor, Azucena; et al.
Revista: European Spine Journal
ISSN 0940-6719  Vol. 20  Nº 2  2011  págs. 338 - 339
Study Design: Prospective, experimental study in animals, approved by the local ethics committee for animal research. Aims: To evaluate and compare the histological changes in myeloradicular structures and paravertebral tissue induced by contact with acrylic cement with and without methotrexate in vertebroplasty in pigs. Material and Methods: Ten female pigs of the Large White¿Landrace breed, weighing 30 kg and divided into two groups: control group, containing five pigs that underwent vertebroplasty with acrylic cement, and methotrexate group, with five pigs that underwent vertebroplasty using cement combined with 1 g of methotrexate. A standard fluoroscopy-guide transpedicular vertebroplasty technique was performed with an 11-G trocar. Cement leak to the prevertebral and epidural muscle tissue was induced in two different lumbar vertebrae; 1 cc of cement was injected per vertebra. Animals were sacrificed at 3 weeks. Spines were removed, the section where tissues were in contact with cement was isolated by dissection, the surface in direct contact with cement was marked with India ink, and specimens were processed by fixation and hematoxylin eosin staining for pos-terior microscopic study. Results: Macroscopic results: In both groups, the cement was distributed in layers surrounding the dural sac. Histological results: In the control group, leakage to the prevertebral musculature with atrophy of muscle fibers, inflammatory infiltrate in areas in contact with cement, epithelial dysplasia, and foreign body reaction in relation to cement particles. In addition, epidural leak with dural thickening and inflammatory reaction only in areas of the dura mater in contact with cement. In the methotrexate group, the same changes as in the control group were observed. Clinical results: Neurological lesion due to cement leak was not produced any of the ten pigs. Conclusions:The tube-like laminar distribution of the cement may explain the fact that there was an absence of paraplegia in the study animals. Contact of the muscle and dura with cement seemed to induce an inflammatory reaction, with cell death, and atrophy and thickening of membranes in some cases. Addition of methotrexate to acrylic cement did not seem to increase the local toxicity of cement alone.
Autores: Aldaz Pastor, Azucena
ISSN 1130-6343  Vol. 35  Nº Supl. 1  2011  págs. 51 - 54
Autores: Zufía López, Laura; Ibáñez, N., ; Aldaz Pastor, Azucena
ISSN 0163-4356  Vol. 33  Nº 4  2011  págs. 521-522
Autores: Zufía López, Laura; Ibáñez, N., ; Aldaz Pastor, Azucena
ISSN 0163-4356  Vol. 33  Nº 4  2011  págs. 542
Autores: Zufía López, Laura; Aldaz Pastor, Azucena; Ibáñez, Nerea; et al.
ISSN 0009-9120  Vol. 43  Nº 4-5  2010  págs. 473 - 482
Autores: Zufía López, Laura; Aldaz Pastor, Azucena; Ibáñez, Nerea; et al.
ISSN 1948-593X  Vol. 2  Nº 2  2010  págs. 35 - 43
An accurate and precise LC method using diode array detection for the determination of voriconazole in human serum/plasma samples has been developed and validated for use in pharmacokinetic studies.A harmonized validation strategy based on the accuracy profiles was used as a suitable tool to guaranty the quality of the results obtained by the use of the analytical validated methodology in a routine setting and to ensure the risk of obtaining the future measurements outside the previously fixed acceptance limits.As pointed recently the FDA, a weighted 1/x2 linear regression model ranging from 0.25 to 10.35 mg/L was selected as the simplest calibration model that maximized the accuracy all over the range. Relative bias was < 7%, assay imprecision was always < 4% and mean extraction recovery from plasma was > 90%. So, accuracy did not exceedthe acceptance limits settled at±15% according to the FDA or Washington conference regulatory requirements for bioanalytical methods.The validated analytical procedure compliants with strongest regulatory standards and their results are rapid and good enough to enable the laboratory to routinely provide useful and accurate pharmacokinetic data in time to adjust patient regimens.
Autores: Alfonso Olmos-García, Matías; Silva González, Álvaro Antonio; Villas Tomé, Carlos; et al.
Revista: European Spine Journal
ISSN 0940-6719  Vol. 19  Nº 1  2010  págs. 157
Autores: Aldaz Pastor, Azucena; Schaiquevich, P.,
Libro:  Individualized drug therapy for patients
2017  págs. 281 - 306
There are still a number of limitations to the full use of therapeutic drug monitoring (TDM) to optimize chemotherapy in oncology. Probably the most important ones arise from the conservatism of clinical practice and the lack of training of physicians in pharmacokinetics (PK). Pharmacogenetics and biomarkers are being incorporated much faster, although the evidence for them is less at present, perhaps because of the lack of training of physicians in quantitative PK approaches rather than remembering clinical facts. Therapy with methotrexate, carboplatin, irinotecan, taxanes, busulfan, 5-fluorouracil, tyrosine kinase inhibitors, and other drugs can be optimized through TDM. In some cases, TDM is used mainly to control toxicity, but it is also useful sometimes to maximize efficacy. Anticancer therapy is best done in a comprehensive manner, incorporating approximate tools for each type and tumor stage. Surgery, radiotherapy, and chemotherapy each have their place. Achieving specific optimal therapeutic target goals for each patient can be feasible, as target ranges of serum drug concentrations are becoming rapidly available. This chapter summarizes the existing evidence concerning the use of TDM in the management of antineoplastic drug therapy.
Autores: Aldaz Pastor, Azucena; Porta, B.,
Libro:  Introducción a las interacciones farmacológicas
2014  págs. 134 - 183
Autores: Aldaz Pastor, Azucena
Libro:  Tratado de productos sanitarios
Vol. 1  2010  págs. 307 - 323
Autores: Aldaz Pastor, Azucena; Milara-Paya, J.,