Renedo, M.J. (María Jesús)
- Publications
- item.page.relationships.isContributorAdvisorOfPublication
- item.page.relationships.isContributorOfPublication
7 results
Search Results
Now showing 1 - 7 of 7
- Comparative Pharmacokinetics, Tissue Distributions, and Effects on Renal Function of Novel Polymeric Formulations of Amphotericin B and Amphotericin B-Deoxycholate in Rats(American Society for Microbiology, 2000) Echevarria, I. (I.); Troconiz, I.F. (Iñaki F.); Renedo, M.J. (María Jesús); Barturen, C. (C.); Dios-Vieitez, M.C. (M. Carmen)The pharmacokinetic profiles of a traditional formulation of amphotericin B (Fungizone) and novel nanosphere and mixed micelle delivery systems developed for amphotericin B were compared and described. Six groups of male Wistar rats received intravenous injections of the different formulations. Plasma and tissue samples were obtained at 11 different times after dosing, with three animals used each time. The amphotericin B concentrations in plasma and tissues were analyzed by high-performance liquid chromatography. The plasma drug concentration-time profiles were best described by a two-compartment model. Models that described the observed single or double peak disposition kinetics in kidney, liver, and spleen were also developed. Parameter estimates from those models show that components of the formulation such as polox- amer 188, which is present in all new formulations, seem to play an important role in the rate of drug uptake by the tissues; in general, the levels of amphotericin B in tissues were increased after the administration of the new formulations compared with those after the administration of Fungizone. The increment in the baseline plasma creatinine level was used as an index of renal function. All formulations increased this baseline value, but the novel formulations exhibited fewer renal effects than Fungizone did. However, a direct relationship between drug exposure in the kidneys and development of renal damage could not be found.
- Humoral immune response in hens naturally infected with Salmonella Enteritidis against outer membrane proteins and other surface structural antigens(EDP Sciences, 2004) Ochoa-Repáraz, J. (Javier); Sesma, B. (Begoña); Gamazo, C. (Carlos); Alvarez, M. (Miguel); Renedo, M.J. (María Jesús); Irache, J.M. (Juan Manuel)A simple procedure for obtaining surface exposed antigens of Salmonella Enteritidis is described. A heat treatment of whole bacteria in saline solution induced the release of small membrane vesicles containing outer membrane components as well as surface appendage components, such as fimbriae and flagellin. The characterization of the structural components of this extract, called HE, was established by SDS-PAGE and immunoblotting using polyclonal and monoclonal specific antibodies. Five major groups of proteins were identified: flagellin, porins, OmpA, SEF21 and SEF14 fimbriae. The immunogenicity of these proteins was studied by immunoblotting with serum samples from naturally infected hens. Flagellin, porins, OmpA, SEF14 and SEF21 fimbriae were immunogenic in the S. Enteritidis infected hens (frequency of reactants: 47.3, 97.3, 64.7, 50.0 and 60.8%, respectively); porins also reacted with sera from non infected hens (66.7%). The immunogenicity of these antigens in infected birds provide promise that they may serve as components of an effective subcellular vaccine for poultry salmonellosis.
- Pharmacokinetic/Pharmacodynamic Modeling of Antipyretic and Anti-Inflammatory Effects of Naproxen in the Rat(Williams & Wilkins, 2001) Flores-Murrieta, F. (Francisco); Josa, M. (Mariona); Troconiz, I.F. (Iñaki F.); Rapado, J. (Javier); Renedo, M.J. (María Jesús); Castañeda-Hernandez, G. (Gilberto); Dios-Vieitez, M.C. (M. Carmen); Perez-Urizar, J. (José)Pharmacokinetic/pharmacodynamic modeling was used to characterize the antipyretic and anti-inflammatory effects of naproxen in rats. An indirect response model was used to describe the antipyretic effects of naproxen after short intravenous infusions. The model assumes that basal temperature (T(a)) is maintained by the balance of fever mediators given by a constant (zero order) rate of synthesis (K(syn)), and a first order rate of degradation (K(out)). After an intraperitoneal injection of lipopolysaccharide, the change in T(a) was modeled assuming an increase in fever mediators described as an input rate function [IR(t)] estimated nonparametrically. An inhibitory E(max) model adequately described the inhibition of IR(t) by naproxen. A more complex model was used to describe the anti-inflammatory response of oral naproxen in the carrageenin-induced edema model. Before carrageenin injection, physiological conditions are maintained by a balance of inflammation mediators given by K(syn) and K(out) (see above). After carrageenin injection, the additional synthesis of mediators is described by IR(t) (see above). Such mediators induced an inflammatory process, which is governed by a first order rate constant (K(IN)) that can be inhibited by the presence of naproxen in plasma. The sigmoidal E(max) model also well described the inhibition of K(IN) by naproxen. Estimates for IC(50) [concentration of naproxen in plasma eliciting half of maximum inhibition of IR(t) or K(IN)] were 4.24 and 4.13 microg/ml, for the antipyretic and anti-inflammatory effects, respectively.
- Pharmacokinetic/pharmacodynamic modeling of the antinociceptive effects of (+)-tramadol in the rat: role of cytochrome P450 2D activity(American Society for Pharmacology and Experimental Therapeutics, 2003) Sayar, O. (Onintza); Troconiz, I.F. (Iñaki F.); Rapado, J. (Javier); Renedo, M.J. (María Jesús); Dios-Vieitez, M.C. (M. Carmen); Segura, C. (Cristina); Garrido, M.J. (María Jesús)In this study the role of cytochrome P450 2D (CYP2D) in the pharmacokinetic/pharmacodynamic relationship of (+)-tramadol [(+)-T] has been explored in rats. Male Wistar rats were infused with (+)-T in the absence of and during pretreatment with a reversible CYP2D inhibitor quinine (Q), determining plasma concentrations of Q, (+)-T, and (+)-O-demethyltramadol [(+)-M1], and measuring antinociception. Pharmacokinetics of (+)-M1, but not (+)-T, was affected by Q pretreatment: early after the start of (+)-T infusion, levels of (+)-M1 were significantly lower (P < 0.05). However, at later times during Q infusion those levels increased continuously, exceeding the values found in animals that did not receive the inhibitor. These results suggest that CYP2D is involved in the formation and elimination of (+)-M1. In fact, results from another experiment where (+)-M1 was given in the presence and in absence of Q showed that (+)-M1 elimination clearance (CL(ME0)) was significantly lower (P < 0.05) in animals receiving Q. Inhibition of both (+)-M1 formation clearance (CL(M10)) and CL(ME0) were modeled by an inhibitory E(MAX) model, and the estimates (relative standard error) of the maximum degree of inhibition (E(MAX)) and IC(50), plasma concentration of Q eliciting half of E(MAX) for CL(M10) and CL(ME0), were 0.94 (0.04), 97 (0.51) ng/ml, and 48 (0.42) ng/ml, respectively. The modeling of the time course of antinociception showed that the contribution of (+)-T was negligible and (+)-M1 was responsible for the observed effects, which depend linearly on (+)-M1 effect site concentrations. Therefore, the CYP2D activity is a major determinant of the antinociception elicited after (+)-T administration.
- Optimization of topical cidofovir penetration using microparticles.(Elsevier, 2002-08) Blanco-Prieto, M.J. (María José); Santoyo, S. (Susana); Renedo, M.J. (María Jesús); Garcia-De-Jalon, E. (Elena); Ygartua, P. (Pilar)Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol® and Precirol® lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween® 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p < 0.01) 14 days after the beginning of the treatment. Our results showed that Tween® 80 coated Compritol® and Precirol® LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo.
- In vitro evaluation of gentamicin released from microparticles(Elsevier, 2002-08) Lecaroz, M.C. (María Concepción); Blanco-Prieto, M.J. (María José); Gamazo, C. (Carlos); Renedo, M.J. (María Jesús); Kunkova, J. (J.)Gentamicin (GEN) is an aminoglycoside antibiotic with a potent antibacterial activity against a wide variety of bacteria. However, its poor cellular penetration limits its use in the treatment of infections caused by intracellular pathogens. One potential strategy to overcome this problem is the use of particulate carriers that can target the intracellular sites of infection. In this study GEN was ion-paired with the anionic AOT surfactant to obtain a hydrophobic complex (GEN–AOT) that was formulated as a particulated material either by the precipitation with a compressed antisolvent (PCA) method or by encapsulation into poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The micronization of GEN–AOT by PCA yielded a particulated material with a higher surface area than the non-precipitated complex, while PLGA NPs within a size range of 250–330 nm and a sustained release of the drug over 70 days were obtained by preparing the NPs using the emulsion solvent evaporation method. For the first time, GEN encapsulation efficiency values of ∼100% were achieved for the different NP formulations with no signs of interaction between the drug and the polymer. Finally, in vitro studies against the intracellular bacteria Brucella melitensis, used as a model of intracellular pathogen, demonstrated that the bactericidal activity of GEN was unmodified after ion-pairing, precipitation or encapsulation into NPs. These results encourage their use for treatment for infections caused by GEN-sensitive intracellular bacteria.
- Liberación controlada de principios activos mediante el empleo de formulaciones galénicas(Servicio de Publicaciones de la Universidad de Navarra, 2001) Goñi-Leza, M.M. (María del Mar); Prior, S. (Sandra); Espuelas, S. (Socorro); Gamazo, C. (Carlos); Renedo, M.J. (María Jesús); Murillo, M. (M.); Vitas, A.I. (Ana Isabel); Irache, J.M. (Juan Manuel)Drugs inside a conventional galenic form are distributed between specific biological targets and other anatomical tissues. With the aim to obtain a more rational and a better therapeutic, one of the most promising possibilities by using the concept of vector- ization: association of an active principle to an appropriate vector with the object to increase its action efficiency and efficacy. By this means, they do not just increase the affinity of the drug to the target but also active principle gets protected from a potentially hos- tile environment (hydrolytic enzymes, acid pH, etc.). The success in the extension of the applications of the vectorización depends more and more of an appropriate design, for what the fundamental objective of this revision will be the one of presenting the general char- acteristics and some of the current applications in these new galenic forms.