Consideraciones prácticas en el manejo de los inhibidores de la bomba de protones / Practical considerations in the management of proton-pump inhibitors

Los inhibidores de la bomba de protones (IBP) son uno de los principios activos más prescritos en España. En las últimas décadas se ha observado un sobreuso de estos fármacos tanto a nivel extrahospitalario como hospitalario que ha producido un aumento importante en el gasto sanitario y un incremento en el riesgo de posibles efectos adversos. Es importante que los profesionales sanitarios se ajusten a las indicaciones admitidas y a las dosis correctas para el empleo de estos medicamentos. Existen en el mercado diferentes tipos de IBP: omeprazol, pantoprazol, lansoprazol, rabeprazol y esomeprazol. El omeprazol es el más antiguo y utilizado, siendo también el más barato. Si bien en la mayoría de las indicaciones terapéuticas en las que se emplean estos medicamentos no se describen diferencias entre los distintos IBP en la curación de las enfermedades, el esomeprazol, IBP de última generación, ha demostrado mayor eficacia en la erradicación del H. pylori y en la curación de la esofagitis grave respecto al resto de IBP. En los últimos años el uso de los fármacos genéricos se ha extendido; este tipo de medicamentos presentan la misma biodisponibilidad que los medicamentos originales. En el caso de los IBP, los pocos estudios comparativos disponibles en la literatura entre los fármacos originales y los genéricos no han demostrado diferencias significativas en la eficacia clínica (AU)

Proton-pump inhibitors (PPIs) are one of the most active ingredients prescribed in Spain. In recent decades there has been an overuse of these drugs in both outpatient clinics and hospitals that has lead to a significant increase in healthcare spending and to an increase in the risk of possible side effects. It is important for health professionals to know the accepted indications and the correct doses for the use of these drugs. On the market there are different types of PPI: omeprazole, pantoprazole, lansoprazole, rabeprazole and esomeprazole. Omeprazole is the oldest and most used PPI, being also the cheapest. Although there are no important differences between PPIs in curing diseases, esomeprazole, a new-generation PPI, has proved to be more effective in eradicating H. pylori and in healing severe esophagitis compared to other PPIs. In recent years the use of generic drugs has spread; these drugs have the same bioavailability than the original drugs. In the case of PPIs, the few comparative studies available in the literature between original and generic drugs have shown no significant differences in clinical efficacy (AU)

Interacciones farmacocinéticas / Pharmacokinetic interactions

Rilpivirina (RPV) es un fármaco perteneciente a la familia de los inhibidores no nucleósidos de la transcriptasa inversa (INNTI), con potente actividad antiviral, aprobado para pacientes naïve, con perfil de efectos secundarios diferente a los INNTI de primera generación. Las interacciones farmacológicas producidas por RPV se deben a su efecto sobre el sistema CYP450, es sustrato de CYP3A4 y ligeramente inductor. Además, in vitro es inhibidor de la glucoproteína-P. RPV presenta interacciones farmacológicas clínicamente significativas, entre las que destacan los inhibidores de la proteasa, a excepción de darunavir y lopinavir potenciados, y los INNTI efavirenz y nevirapina. La toma de RPV junto con fármacos que aumentan el pH gástrico, como omeprazol, o los que inducen el CYP3A4, como rifampicina, puede causar reducciones significativas en las concentraciones de RPV y está contraindicada. El uso concomitante de RPV con un inhibidor del CYP3A4, por ejemplo claritromicina, puede provocar aumento de las concentraciones de RPV. Se recomienda la administración de RPV con alimentos para obtener mejor absorción y valores plasmáticos adecuados

Rilpivirine (RPV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been approved for use in treatment-naïve patients and which has potent antiviral activity. Its adverse effects profile differs from that of first-generation NNRTs. The pharmacological interactions produced by RPV are due to its effects on the CYP450 system; RPV is a substrate and mild inducer of CYP3A4. Moreover, in vitro, RPV inhibits glycoprotein-P. RPV has clinically significant pharmacological interactions, especially with protease inhibitors (except boosted darunavir and lopinavir) and the NNRTIs efavirenz and nevirapine. Coadministration of RPV with drugs that increase gastric pH, such as omeprazole, or those inducing CYP3A4, such as rifampicin, can significantly reduce RPV concentrations and is contraindicated. The concomitant use of RPV with a CYP3A4 inhibitor (such as clarithromycin) can increase RPV concentrations. Administration of PRV with food is recommended to obtain better absorption and adequate plasma values

Determination of lansoprazole in human plasma by rapid resolution liquid chromatography-electrospray tandem mass spectrometry: application to a bioequivalence study on Chinese volunteers.

A simple, sensitive and rapid LC/MS/MS method was developed for the quantification of lansoprazole in human plasma. After a simple sample preparation procedure by one-step protein precipitation with acetonitrile, lansoprazole and the internal standard bicalutamide were chromatographed on a Zorbax SB-C(18) (3.0 mm x 150 mm, 3.5 microm, Agilent) column with the mobile phase consisted of methanol-water (70:30, v/v, containing 5 mM ammonium formate, pH was adjusted to 7.85 by 1% ammonia solution). Detection was performed on a triple quadrupole tandem mass spectrometry by multiple reaction monitoring (MRM) mode via negative eletrospray ionization source (ESI(-)). The lower limit of quantification was 5.5 ng/mL, and the assay exhibited a linear range of 5.5-2200.0 ng/mL. The validated method was successfully applied to investigate the bioequivalence between two kinds of preparation (test vs. reference product) in twenty-eight healthy male Chinese volunteers.

A novel option in proton pump inhibitor dosing: lansoprazole orally disintegrating tablet dispersed in water and administered via nasogastric tube.

BACKGROUND: Lansoprazole orally disintegrating tablet, which rapidly disintegrates on the tongue or in water, provides a dosing alternative for patients with difficulty in swallowing. Gastric and nasogastric tubes are increasingly placed in patients with more severe swallowing disorders. AIM: This study assessed the pharmacokinetic profile of lansoprazole orally disintegrating tablet dispersed in a small volume of water and administered through a small-bore nasogastric tube. METHODS: Forty healthy adult men and women (18-43 years) received two single 30 mg lansoprazole orally disintegrating tablet doses (one administered directly onto the tongue without water, and one dispersed in water and administered via nasogastric tube) in a randomized, crossover fashion. RESULTS: The total plasma exposure to lansoprazole was comparable following both dosing regimens; mean AUC values for the lansoprazole orally disintegrating tablet nasogastric dispersion were < or =8.6% greater than those for the intact lansoprazole orally disintegrating tablet. Lansoprazole Cmax for the lansoprazole orally disintegrating tablet nasogastric dispersion was 20.9% greater than that for the intact lansoprazole orally disintegrating tablet, a difference of no clinical significance. CONCLUSIONS: Dispersion of the lansoprazole orally disintegrating tablet in a small volume of water and administering via nasogastric tube does not reduce the pharmacokinetic profile of the intact lansoprazole orally disintegrating tablet. This alternative dosing method may be useful in patients with nasogastric or gastric tubes.

Pharmacokinetic interactions between omeprazole/pantoprazole and clarithromycin in health volunteers.

The association omeprazole/clarithromycin is of current wide use in the treatment of Helicobacter pylori associated gastroduodenal ulcer. This combination may result in increased levels of omeprazole with potential interactions with commonly associated drugs. Kinetic/metabolic changes occurring after omeprazole/clarithromycin were compared to those occurring after pantoprazole/clarithromycin in healthy volunteers. Eight healthy volunteers, all males, age 25-34 years, all EM for CYP2C19, participated in a randomized, double blind crossover study in two periods of 7 days, separated by a 14-day washout. In each treatment period, subjects took either omeprazole 20mg b.i.d. together with clarithromycin 500 mg b.i.d., or pantoprazole 40 mg b.i.d. with the same dose of the antibiotic. The pharmacokinetic parameters of omeprazole and pantoprazole were compared to those after intake of both agents alone. Kinetics of unchanged clarithromycin was evaluated at the end of the two periods. The mean value of the area under the plasma concentration versus time curve (AUC) of unchanged omeprazole increased almost two-fold after concomitant administration of clarithromycin; the average 5-OH-omeprazole AUC was instead significantly reduced by 42%. Omeprazole clearance and volume of distribution were reduced significantly by 75 and 56%, respectively, after administration of the drug with clarithromicyn. No significant changes of the kinetic of pantoprazole and metabolites were observed. Kinetics of clarithromycin did not differ after the two associated treatments. The administration of clarithromycin with two different proton pump inhibitors indicates that the antibiotic can markedly increase omeprazole, not pantoprazole, levels. This observation may result in a better therapeutic response to omeprazole, but it may also potentially affect either the metabolism of CYP3A4 substrates or interfere with the absorption of drugs requiring an intact gastric digestion system.

Radioterapia y tratamientos de soporte. Protección gastrointestinal. Antieméticos

No disponible

Proton pump inhibitors in the elderly population.

Accurate diagnosis and effective treatment of acid-related diseases, including gastro-oesophageal reflux disease (GORD), are important health care priorities, particularly in the elderly. Both the prevalence and severity of GORD are increased in older individuals. The reason for the age-related increase in the prevalence of GORD is not completely understood, but it appears to result from both age-related changes in physiology and effects of the medications often taken by older people. The diagnosis of GORD in the elderly is also difficult because of its potential atypical presentation in these patients, as well as the overlap between GORD symptoms and those of other chronic conditions, including coronary artery disease and chronic obstructive pulmonary disease. Proton pump inhibitors (PPIs) are now considered the treatment of choice for patients with GORD, and these drugs have excellent efficacy and safety profiles. One of the newer drugs in this class, rabeprazole, may be particularly suited for use in older patients. Rabeprazole requires no dosing adjustment in the elderly or in patients with renal insufficiency or mild-to-moderate hepatic disease. It is also relatively free of clinically significant drug-drug interactions, which strongly differentiates rabeprazole from omeprazole, the prototype PPI. Overall, the clinical and pharmacokinetic profiles for rabeprazole suggest that it is an excellent first choice for the management of older patients with GORD.

Pharmacokinetics and pharmacodynamics of esomeprazole, the S-isomer of omeprazole.

BACKGROUND: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid-related diseases. AIM: To examine the pharmacokinetics and pharmacodynamics of esomeprazole. METHODS: In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin-stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5. RESULTS: The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin-stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin-stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5). CONCLUSIONS: The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.