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La mayoría de los ciudadanos europeos no cumplen con un adecuado aporte de calcio y vitamina D en sus dietas, por lo que los suplementos de ambos pueden ayudar a cubrir las necesidades. El déficit de vitamina D puede conducir a una menor absorción de calcio, un aumento del remodelado óseo y un incremento de la pérdida de masa ósea; además, el déficit de vitamina D reduce la función muscular y aumenta el riesgo de caidas. El carbonato de calcio es la forma farmacéutica de uso más común, debido a su perfil coste/eficacia, de administrar suplementos de calcio en nuestro medio. Otras sales como el lactato y gluconato presentan una menor concentración del elemento y son poco prácticas. El objeto del presente artículo es poner de manifiesto la relevancia de la asociación calcio-vitamina D, su protagonismo en la prevención y tratamiento de la osteoporosis, así como las formas farmacéuticas más frecuentes y útiles para su uso clínico.

Background: Enemas are used by individuals with constipation and are of-ten required before certain medical diagnostic procedures and surgical interventions. However, abnormalities in serum electrolyte concentrations have been associated with enema use.Objective: The aim of this study was to determine the changes in serum electrolyte concentrations (phosphorus, calcium, sodium, and potassium) and urinary phosphorus elimination after the administration of a sodium phosphate enema.Methods: Healthy volunteers aged 35 to 70 years were eligible for this open-label, randomized, controlled, 2-period, crossover clinical trial at the Clinical Research Unit of the University Hospital of Navarra, Pamplona, Spain. The study comprised 2 one-day periods separated by a 7-day washout. All subjects were randomly assigned in a 1:1 ratio to 1 of 2 study sequences: (1) a single dose of Enema Cased 250 mL in the first period followed by no treatment (control) in the second period, or (2) no treatment in the first period followed by a single dose of the study drug in the second period. The sequence of treatment was assigned using a randomization table that was prepared before the beginning of the study. Serum concentrations of phosphorus, sodium, potassium, and calcium were measured in both periods. Urinary phosphorus elimination was measured for 12 hours after enema administration (Ae[0-12]) in a subset of the subjects in the second period. Adverse events (AEs) were monitored by the investigators throughout the study. Normal ranges for the electrolytes were as follows: phosphorus, 2.5 to 5 mg/dL; calcium, 8.5 to 10.5 mg/dL; sodium, 135 to 145 mEq/L; and potassium, 3.5 to 5 mEq/L.Results: Twenty-four subjects (12 men, 12 women; mean [SD] age, 47.8 [9.6] years [range, 36-68 years]) participated in the study. All of the subjects were white and none were smokers. Twelve hours after enema administration, mean serum phosphorus and sodium concentrations increased by a mean of 1.18 mg/dL and 1.32 mEq/L, respectively (both, P < 0.001). Mean serum phosphorus concentrations were above the upper limit of normal (5 mg/dL) at 30 and 60 minutes after enema administration. In all subjects the values returned to normal within 4 hours after enema administration; a meal was provided after a 3-hour fast. Four subjects (16.7%) had >/=>1 serum phosphorus concentration measurement >/=7 mg/dL, a value that is considered serious hyperphosphatemia. A statistically significant correlation was found between phosphorus [C][max] and enema retention time (r[2] = 0.452; P < 0.001). No abnormal serum concentrations were obtained for the other electrolytes measured. Phosphorus Ae[0-12] was increased after enema administration by 86% (P < 0.001). No serious AEs were observed, although 13 AEs were reported in 9 subjects. None of the changes in serum electrolyte concentrations were associated with clinical symptoms.Conclusions: Administration of an enema containing 250 mL of sodium phosphate was associated with serum phosphorus concentrations of >/=7 mg/dL in 16.7% of the healthy subjects who participated in the study; however, none of those subjects experienced hypocalcemia. Enema retention time was significantly correlated with the degree of phosphatemia. [ABSTRACT FROM AUTHOR]

The objective of the present article is the review of the most important therapeutic innovations in the treatment of multiple myeloma in terms of efficacy and cost-effectiveness. Besides autologous transplant with peripheral-blood stem-cell, thalidomide establishes as one of the most powerful therapeutic tools in induction and maintenance treatment and together with lenalidomide and bortezomib as therapy for relapsing/refractory multiple myeloma. Considering, the last named situation thalidomide can be an adequate therapeutical option in combination with dexamethasone. Under a strictly pharmacoeconomic point of view, lenalidomide and bortezomib seem to be additional alternatives in patients previously treated with thalidomide.

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.

Objective: Our objective was to evaluate the effect of CYP2D6 phenotype in the enantioselective metabolism of tramadol in Spanish healthy human volunteers., Methods: A single oral 100mg dose of racemic tramadol was administered to five subjects who were poor metabolizers (PMs) and 19 subjects who were extensive metabolizers (EMs), whose phenotypes were determined by the use of the racemic tramadol metabolic rate. The pharmacokinetic parameters were estimated from plasma concentrations of the enantiomers of tramadol and their main phase I metabolites, O-desmethyltramadol (M1) and N-desmethyltramadol (M2). Epinephrine plasma concentrations were also determinated., Results: The plasma concentrations of both tramadol enantiomers were consistently higher in PMs than in EMs of CYP2D6, with 1.98- and 1.74-fold differences in the mean area under the plasma concentration-time curves (AUC), respectively. The values for oral clearance of (+)- and (--)-tramadol were 1.91- and 1.71-fold greater in PMs, which were related to differences in both O-desmethylation and N-desmethylation in the two CYP2D6 metabolizer phenotypes. The mean AUC values of (+)-M1 and (--)-M1 were 4.33- and 0.89-fold greater in EMs, and it was related to similar differences in the formation rate constant. On the other hand, the differences were 7.40- and 8.69-fold greater in PMs for M2 enantiomers due to the involvement of CYP2D6 in their subsequent biotransformation. The time course of epinephrine systemic concentrations was completely different between both groups of metabolizers. In EMs plasma concentrations of epinephrine increased after tramadol administration whereas in PMs no effect was observed., Conclusions: The polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol enantiomers. The N-desmethylation pathway was indirectly affected by CYP2D6 phenotypic differences. Epinephrine showed a good correlation with the pharmacokinetics of the opioid component of tramadol, (+)-M1 and was found to be useful for its pharmacodynamic profiling.

The kinetics of tramadol enantiomers are stereoselective when doses of the racemic drug are given orally. To document whether the route of administration determines the stereoselective kinetics of tramadol enantiomers, healthy volunteers received 100 mg oral or intravenous doses of racemic tramadol, and serial blood samples were obtained to assay tramadol enantiomers and their main phase I metabolites, O-demethyltramadol and N-demethyltramadol. To assess accurately the involvement of their metabolites in the pharmacokinetics of tramadol, it is essential to determine the rate and extent of the formation of the enantiomers of these metabolites. A simultaneous pharmacokinetic model describing the plasma concentration-curves of the generated metabolites and the parent compounds after intravenous and oral drug administration is developed and presented. Tramadol and O-demethyltramadol were the major compounds detected in plasma after intravenous administration. Nevertheless, the N-demethylation of tramadol showed a significant increase when the oral route was used. After both oral and intravenous doses, the kinetics of the tramadol enantiomers were stereoselective. The AUC for (R )-(+)-tramadol was greater than the AUC for (S)-(-)-tramadol. The formation of N-demethyltramadol also was enantioselective after oral administration of racemic tramadol, with a greater AUC for (R)-(+)-N-demethyltramadol than for (S)-(-)-N-demethyltramadol. In the opposite form, (S)-(-)-O-demethyltramadol was formed faster than (R)-(+)-O-demethyltramadol. The metabolism of tramadol was also route-dependent with a different enantiomeric ratio for tramadol and its main phase I metabolites after intravenous and oral administration. The disposition of N-demethyltramadol was concentration-dependent., (Copyright 2006 John Wiley & Sons, Ltd.)

Introduction: A short antibiotic regimen is recommended for the treatment of uncomplicated lower urinary tract infection. Nevertheless, the treatment to follow in other situations is not so clearly defined. When the person affected by lower urinary tract infection is not a young woman, it is recommended to treat at least 7 days, and quinolones or cotrimoxazole are the antibiotics most often used. However, because of the frequency of drug resistance in this type if infection, it is advisable to apply antibiotics with lower rates of resistance, such as fosfomycin trometamol, for longer treatment periods than the often-used single dose., Methods: Using the data on urinary elimination of fosfomycin after a single dose obtained in a prior study in healthy volunteers, we simulated the urinary concentrations of this antibiotic following administration of two doses. In addition, we calculated the interval of administration required to achieve urinary concentrations greater than 16 mg/L, the critical concentration of sensitivity for Escherichia coli, one of the most commonly implicated microorganisms in these infections., Results: Fosfomycin concentrations in urine persisted above the defined cut-off for 161 hours after administration of two 3-g doses of fosfomycin trometamol, 72 hours apart. This implied an efficacy time of 66% in a period of 7 days., Conclusion: From the pharmacokinetic viewpoint, the optimum dosage of fosfomycin trometamol to achieve appropriate urinary concentrations along 7 days is administration of two 3-g doses, 72 hours apart.

Objective: Ibuprofen arginate is a salt formulation of ibuprofen designed to reach target concentrations rapidly. The primary objective of this study was to compare the 12-h pharmacokinetic profile of S(+)-ibuprofen following administration of single doses of ibuprofen arginate (600 mg) and dexibuprofen (400 mg) in healthy volunteers., Methods: Twenty-four volunteers were recruited into an open-label, randomised, two-period, single-centre study with crossover design., Results: Both treatments were well tolerated. Ibuprofen arginate and dexibuprofen showed similar bioavailability for S(+)-ibuprofen. Compared with dexibuprofen, ibuprofen arginate demonstrated a 45% higher maximum concentration (C(max)), and a time to peak concentration (T(max)) 2 h sooner., Conclusion: Ibuprofen arginate approaches maximum concentrations of S(+)-ibuprofen faster and higher than dexibuprofen.

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.

We developed and validated an accurate, sensitive, precise and rapid HPLC method with UV detection for the determination of sirolimus in blood samples from renal, cardiac and hepatic transplants. This method overcomes most of the problems related to previously published assays using a narrow-bore column with base deactivated C18 reversed phase. Whole blood samples were purified by a combination of a precipitating blood matrix with zinc sulphate and a single step liquid-liquid extraction with acetone and 1-chlorobutane. Calibration curves (range 2.5-150 ng/ml), were linear with coefficients of correlation better than 0.996. The relative standard deviation was determined to be less than 8%. The present method has also been validated by a reference laboratory (St. George's Hospital Medical School, London, UK). More of 300 clinical samples have been analysed with this method.

This paper describes a bioanalytical method involving a simple liquid-liquid extraction for the simultaneous HPLC determination of the enantiomers of tramadol, the active metabolite O-desmethyltramadol (M1), and the other main metabolite N-desmethyltramadol (M2) in biological samples. Chromatography was performed at 5 degrees C on a Chiracel OD-R column containing cellulose tris(3,5-dimethylphenylcarbamate) as chiral selector, preceded by a achiral end-capped C8 column (LiChrospher 60-RP-selected B 5 microm, 250 mm x 4 mm). The mobile phase was a mixture of phosphate buffer containing sodium perchlorate (1 M) adjusted to pH 2.5-acetonitrile-N,N-dimethyloctylamine (74.8:25:0.2). The flow rate was 0.5 ml/min. Fluorescence detection (lambda(ex) 200 nm/lambda(em) 301 nm) was used. Fluconazol was selected as internal standard. The limit of quantitation of each enantiomer of tramadol and their metabolites was 0.5 ng/ml (sample size = 0.5 ml). The chiral conditions and the LC optimisation were investigated in order to select the most appropriate operating conditions. The method developed has also been validated. Mean recoveries above of 95% for each enantiomer were obtained. Calibration curves for tramadol enantiomers (range 1-500 ng/ml), M1 enantiomers (range 0.5-100 ng/ml), and M2 enantiomers (range 0.5-250 ng/ml) were linear with coefficients of correlation better than 0.996. Within-day variation determined on four different concentrations showed acceptable values. The relative standard deviation (R.S.D.) was determined to be less than 10%. This method was successfully used to investigate plasma concentration of enantiomers of tramadol, O-desmethyltramadol and N-desmethyltramadol in a pharmacokinetic study.

Antimicrobials with specific activity against Gram-positive cocci (glycopeptides, oxazolidinones and streptogramins) have pharmacokinetic differences that are important to know. Linezolid and teicoplanin can be administered extravascularly due to their good bioavailability, allowing their use as sequential therapy in patients requiring prolonged treatment. All of these antimicrobials have an adequate distribution in extracellular tissues, even teicoplanin, due to the balance between the fraction that is bound and unbound to plasma proteins and its long terminal half-life. As the elimination of glycopeptides is almost exclusively renal, it is necessary to perform a posology adjustment in patients with renal failure. Quinupristin/dalfopristin and linezolid are metabolized by the liver, but CYP450 is only involved in streptogramin elimination.

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.

A sensitive high-performance liquid chromatographic assay for the quantitative determination of gemfibrozil is described in this work. Ibuprofen was used as internal standard. The assay involved a single cyclohexane extraction and LC analysis with fluorescence detection. Chromatography was performed at 40 degrees C on a Hypersil ODS column. The mobile phase was a mixture of a solution of phosphoric acid 0.4% and acetonitrile (45:55). The method was validated. The detection limit of this method was 0.025 microg ml(-1); only 0.5 ml of the plasma sample was required for the determination. The calibration graph was linear from 0.05 to 0.5 microg ml(-1) and required a cubic equation from 0.5 to 30 microg ml(-1). Intra and inter-day precision (C.V.) did no exceed 15%. Mean recoveries were of 90.15+/-6.9% (C.V.'s<8%) for gemfibrozil and 93.10% for ibuprofen Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received gemfibrozil by oral route.

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.