35 research outputs found
Anfotericina B forma liposómica: un perfil farmacocinético exclusivo. Una historia inacabada.
Amphotericin B in its lipid formulation continues to be the reference drug in the treatment of systemic fungal infections despite the time elapse since the development of this compound. The absence of fungal resistance, pharmacokinetics, and the better tolerability profile as compared with the remaining formulations of amphotericin B are sufficient reasons to justify its prominent therapeutic role. The liposome containing liposomal amphotericin B is very stable in relation to the presence of cholesterol and phospholipids are not thermolabile, so that free amphotericin B is almost inexistent (<1%), which explains the reduced incidence of effects related to the drug administration, and a reduction in the incidence of nephrotoxicity (half than that with amphotericin B lipid complex) and that even in some studies at doses of 1 mg/kg has been shown to be negligible. This profile explains the very high plasma drug concentrations and the reduced distribution volume and clearance, with a very prolonged elimination half-life. There are evidences showing that the liposome through amphotericin B is capable of binding to ergosterol present in the fungal membrane and only at this moment would be the antifungal released to exert its pharmacological effects
Infecciones más comunes en el paciente trasplantado
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 trasplant 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 trasplantation
by active immunization through vaccine administration
to the patient and to people in the milieu
and continue after trasplantation with prophylaxis or
pre-emptive therapy. The importance of infectious
diseases in the evolution and prognosis of trasplant
recipients gives a special meaning to the understanding
of associated infections, their clinical expression
and ways of prevention and treatment
Comparative pharmacology of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia
There are 5 BCR/ABL tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia
(CML): bosutinib, ponatinib, imatinib, nilotinib and dasatinib. The availability of several therapeutic
options raises the possibility of individualizing patient treatment. When evaluating patients’ individual
pharmacological profiles, it is important to take into account the differences in the chemical structures of
the drugs. Bosutinib, which has a unique interaction and safety profile, is a quinazoline, unlike the other
TKIs that have a pyrimidine structure. All 5 TKIs inhibit the BCR/ABL tyrosine kinase, although only
ponatinib is active against the strains expressing the T315I mutation. In addition, the 5 TKIs are generally
non-selective drugs that can also inhibit other tyrosine kinases, such as cKIT or PDGFR, leading to both
benefits in the treatment of some gastrointestinal tumors as well as additional adverse events. These drugs
are orally administered and show moderate bioavailability, a large volume of distribution, high protein
binding, and elimination after intense metabolism involving various Cytochrome P450 (CYP). They are
also substrates of transport proteins and interact with inducers and inhibitors. All TKIs, except bosutinib,
can inhibit the activity of transport proteins, leading to important drug interactions. As such, bosutinib is
the drug with the better pharmacological profile. There is a close relationship between drug concentration
and the beneficial/toxic effects of imatinib, nilotinib, and dasatinib. Therefore, plasma levels should be
monitored to optimize patient treatment. Currently, there is no information for ponatinib. Overall, there
is a high incidence of adverse events; although these do not usually lead to treatment discontinuation.
All 5 TKIs have a similar safety profile; however, each TKI has unique adverse events. Pharmacological
differences can identify the drug that is best suited to each patient, helping optimize CML therapy
FarmacologÃa de los azoles
Azole antifungals have different pharmacokinetic characteristics: complete oral
absorption for Voriconazole, and to a lesser extent for fluconazole.
The absorption of posaconazole and itraconazole increases with food intake.
All of them have high tissue distribution with low plasma concentrations,
especially low in the case of posaconazole and itraconazole. Posaconazole
and itraconazole have high plasmatic protein binding and consequently both
have a very low free fraction. Elimination of azole antifungals is through a
metabolic pathway with CYP450 isoenzymes, and has a non linear
pharmacokinetics with a high risk of interation with other drugs since azoles
have the ability of CYP450 isoenzymes inhibition. Possibly the parameter that
defines more precisely their efficacy is AUIC with an optimum value near 20,
although cut-off values must be defined since some azoles may have difficulty
to reach this value
Levofloxacino. Experiencia clÃnica en tratamientos de larga duración de infecciones osteoarticulares
Se ha realizado un estudio con el fin de evaluar la eficacia y la tolerancia de la administración de larga duración de levofloxacino en el tratamiento de infecciones osteoarticulares. Se incluyeron 50 pacientes con una previsión inicial de realizar tratamiento antibiótico de duración superior a cuatro semanas, durante los años 1999-2001. El 46% de los pacientes eran varones y recibieron tratamiento con levofloxacino durante una media de 122,8 dÃas. En el 83,7% de los pacientes evaluables (41/49 pacientes) la evolución fue satisfac- toria, por la desaparición o mejorÃa de la infección. Se realizaron controles médicos y analÃticos seriados, sin objetivarse en ellos alte- raciones significativas. Cinco de los pacientes estudiados presenta- ron un total de 7 efectos adversos: molestias digestivas (3), micosis oral (1), petequias (1), parestesias (1) y erupción pruriginosa(1). En tres de ellos se suspendió el tratamiento por este motivo. Se concluye que levofloxacino es un fármaco eficaz y bien tolerado, por ello puede ser utilizado en el tratamiento de infecciones que requieran terapia prolongada.We evaluated the efficacy and safety profile of the long-term administration of levofloxacin in osteoarticular infections. For this purpose, 50 patients were included during the years 1999 to 2001 on an initial estimation to be under treatment with this antibiotic for at least 4 weeks. Forty six percent (46%) of patients were male and received treatment during a mean-time of 122.8 days. In forty one of a total of forty nine evaluable patients (83.7%) outcome was considered satisfactory with a total recovery or improvement of disease. Clinical and analytical series of examinations were performed, with no significant abnormalities being observed. Five (5) patients presented a total of 7 adverse events: gastrointestinal intolerance (3), oral mycosis (1), petechia (1), parestesia (1) and pruriginous rash(1). Only in three cases interruption of therapy was considered necessary. In conclusion, levofloxacin presents an adequate efficacy and is a well-tolerated therapy; both characteristics make it an appropriate treatment for those infections that require long-term therapy
Estudio de la eficacia antihipertensiva y tolerancia del bopindolol (LT 31-200) en pacientes hipertensos
Se ha realizado un estudio abierto con dosis crecientes de bopindolol, beta-bloqueante no selectivo de vida media larga, en pacientes con hipertensión arterial leve y moderada para valorar la eficacia y seguridad del tratamiento a corto y largo plazo.
Se incluyeron 20 pacientes (12 mujeres y 8 varones) con edades comprendidas entre 36 y 62 años (x ± SD 51,6 ± 7,6) cuyas TA fueron superiores a 160 mm de Hg para la sistólica y entre 90 y 125 mm de Hg para la diastólica (x ± SD 165 ± 7,2 y 102,6 ± 6,7 respectivamente). Todos los pacientes fueron informados de las caracterÃsticas del estudio y dieron su consentimiento por escrito para participar en el mismo.
Tras la anamnesis y exploración fÃsica correspondientes se realizaron pruebas analÃticas y complementarias con la finalidad de descartar patologÃa asociada.
Diecinueve de los veinte pacientes (95 %) respondieron satisfactoriamente tras 20 semanas de tratamiento con bopindolol oral una vez al dÃa observándose diferencias estadÃsticamente significativas (p ≤ 0,001) a la 4.ª semana de tratamiento respecto a las cifras tensionales del perÃodo placebo (TA sistólica media 141,2 ± 17, TA diastólica media 87,22 ± 6,5).
Resultados similares fueron obtenidos respecto a la frecuencia cardiaca. Las cifras de HDL-colesterol aumentaron significativamente (p ≤ 0,001) al igual que el cociente HDL-colesterol/colesterol total. No hubo variaciones importantes respecto al resto de parámetros estudiados.
La tolerancia clÃnica fue buena en general, aunque algunos pacientes refirieron cefalea, somnolencia y náuseas, de intensidad moderada que no precisaron suspender el tratamiento
Bioavailability of two oral fentanyl transmucosal formulations in healthy volunteers: an open-label, crossover, randomised study.
Introduction: Oral transmucosal fentanyl citrate (OTFC)
was the first product specifically designed for the treatment of
breakthrough pain. It is formulated as a sweetened lozenge on
a plastic handle (stick) and it is self-administered by the patient,
allowing the modulability or flexibility in dosing.
Objectives: To prove bioequivalence of a test (T) OTFC product compared to the reference (R) formulation.
Material and methods: Open-label, crossover, randomized,
single-dose bioequivalence study in healthy volunteers, with two
study periods and two sequences, with a washout period of at
least 10 days. On each study day, subjects received 400 μg of
fentanyl. They were instructed to rub the tablet gently against
the buccal mucosa and not to suck on or chew it, and the investigators controlled each administration to ensure that it was
consumed during 15 minutes. Given the high pharmacokinetic
variability, a two-stage design was established and bioequivalence decision was based on 94.12% confidence intervals of Cmax
and AUC0-t geometric means ratio.
Results: 36 subjects completed the study according to
the protocol. Mean Cmax were similar with both formulations
(814.78 pg/ml for T and 781.83 pg/ml for R) and were attained at the same time (40 min. for T and 50 min. for R), and their
bioavailability was also very close (AUC0-t: 3920.12 pg.h/ml
for T and 3679.39 pg.h/ml for R). Bioequivalence was confirmed for the two primary parameters, Cmax and AUC0-t. No
period or sequence effects were observed in any parameter.
As bioequivalence was proved in the first phase of the study, it
was not necessary to proceed to the second stage. The estimated intraindividual variability was 24.66% and 19.01%, respectively for T and R formulations. Both formulations were well
tolerated; 15 mild adverse events were reported.
Discussion: The test OTFC product is bioequivalent to the
reference one and therefore interchangeable when used clinically. OTFC administration provides faster fentanyl absorption
than enteral route and the rate of absorption can be modulated
by the administration technique, providing a unique flexibility
among all breakthrough pain treatments. The results showed
a fast time to maximum concentrations (tmax), in accordance
with those originally reported for the reference product, probably favoured by the strict administration technique. Proper
patient education is essential to optimize the use of OTFC, as
well-trained patients can take advantage of its flexibility to selfcontrolling pain relief
Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria
Bilastine is a second generation antihistamine indicated for the treatment of seasonal or perennial allergic rhinoconjunctivitis and chronic urticaria with a daily dose of 20 mg, in adults and children over 12 years of age. The efficacy of bilastine has been shown to be similar to that of the comparator drugs for the control of the nasal and nonnasal symptoms of allergic rhinoconjunctivitis, while also showing a subjective improvement in the quality of life and in overall clinical impression. For chronic urticaria the symptoms (itching and the development of papules) lessens from the second day of treatment onwards, in a similar way to other antihistamines used as comparators. Bilastine should not be administered at meal times to avoid interference with the absorption process. It is not distributed to the central nervous system, is scarcely metabolized, and elimination is through the kidneys and feces, with a 14-hour elimination half-life. It has no effect on cytochrome P450. During clinical development, bilastine was shown to be a drug that is adequately tolerated, with a similar effect to placebo with regard to drowsiness and changes in heart rate. In relation to its use, headaches were the most frequent adverse effect to be reported. No cardiotoxic effects have been observed, and the therapeutic dose does not alter the state of alertness
Posibles indicaciones del tratamiento de las enfermedades autoinmunes con tacrolimus
Tacrolimus is an immunosuppressive drug used most successfully as a primary drug to suppress the rejection of transplants. Tacrolimus may also be useful as a novel therapy for autoimmune disease. There are various reports in the bibliography about the use of tacrolimus in the treatment of some autoimmune diseases: inflammatory bowel disease, autoimmune hepatitis, cutaneous, neurologic, renal, endocrine or eye disease. In this review of more than 130 papers, we discuss the rationale for the use of tacrolimus in autoimmune disease and report the clinical experience with the drug in the management of a variety of autoimmune diseases. But, although there are a lot questions that require future research (dose, duration of treatment, when to begin tacrolimus treatment, how to monitor it, etc.), there is also wide experience with tacrolimus in the treatment of this type of disease