Effect of Obesity and Roux-En-Y Gastric Surgery on Omeprazole Pharmacokinetics.

INTRODUCTION: The prevalence of obesity is increasing globally. The principal aim was to evaluate whether gastric bypass surgery modifies the bioavailability and pharmacokinetic (PK) parameters of omeprazole. METHODS: Controlled, open-label, bioavailability clinical trial in patients undergoing Roux-en-Y gastric bypass (RYGB). Healthy patients with obesity (body mass index >35) were included and assessed for omeprazole PKs before and after RYGB (1 and 6 months). PK sampling was done at baseline and several times up to 12 h after drug dosing. Pre- and post-surgery parameters were compared using paired ANOVA or Wilcoxon tests, and control versus cases using ANOVA or Mann-Whitney tests. Given the post-surgery change in body weight, parameters were corrected by dose/body weight. RESULTS: Fourteen case and 24 control subjects were recruited; 92% were women (N = 35/38). In patients who underwent RYGB, maximum plasma concentration (Cmax) was significantly reduced at 1 and 6 months after surgery compared with presurgery values (p = 0.001). Regarding the AUC, the values are lower at 1 and 6 months after surgery than at baseline (p < 0.001). The drug clearance was also increased in the first month after surgery. No differences were found between patients 6 months after surgery and controls. Cmax and AUC corrected by dose/body weight were significantly different between the baseline surgery subjects and controls. Discusion/Conclusions: Omeprazole bioavailability is reduced in patients with obesity at 1 and 6 months after RYGB. However, omeprazole PK parameters 6 months after RYGB are similar to control subjects, and thus no dose correction is required after RYGB for a given indication.

Effect of Roux-en-Y gastric surgery on ciprofloxacin pharmacokinetics: an obvious effect?

PURPOSE: To evaluate pharmacokinetic parameters of ciprofloxacin in patients undergoing Roux-en-Y gastric surgery (RYGS). METHODS: Controlled, single-dose, open-label study in patients undergoing RYGS. Healthy overweight/obese patients 18-60 years old were included. The assessment was performed once in control patients and three times in case patients (before surgery and 1 and 6 months after surgery). In each visit, the subjects received a single oral dose of ciprofloxacin 500 mg. Venous blood samples were obtained at baseline and 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 8 and 14 h after ciprofloxacin intake. Pre- and post-surgery variables were compared using paired ANOVA or the Wilcoxon tests and control vs cases using ANOVA or Mann Whitney. Given the post-surgery change in body weight, the parameters were corrected by dose (mg)/body weight (kg). The analysis was performed using SPSS. RESULTS: Ciprofloxacin Cmax was significantly reduced 1 month after surgery (1840.9 ± 485.2 vs 1589.6 ± 321.8 ng/ml; p = 0.032) but not 6 months after. Cmax on the sixth month was lower than Cmax in control group (2160.4 ± 408.6 vs 1589.6 ± 321.8 ng/ml; p < 0.001). After correcting by the dose (mg)/patient's body weight, both Cmax and AUClast showed significant decrease 1 and 6 months after surgery: Cmax, 289.1 ± 65.3 and 263.5 ± 52.1 (ng/ml)/(dose (mg)/weight (kg)) respectively vs 429.3 ± 127.6 (ng/ml)/(dose (mg)/weight (kg)) at baseline; AUC, 1340.6 ± 243.0 and 1299.2 ± 415.4 (h × ng/ml)/(dose (mg)/weight (kg)) respectively vs 1896.7 ± 396.8 (h × ng/ml)/(dose (mg)/weight (kg)) at baseline. Cmax 1 month post-surgery showed lower values than the control group (375.4 ± 77.4 vs 263.5 ± 52.1 ng/ml; p < 0.001). CONCLUSION: Ciprofloxacin absorption is impaired 1 month and 6 months after RYGS. The effect on Cmax and AUClast faded on the sixth month due to weight loss. It is no necessary to modify the doses of ciprofloxacin in these patients.

Update on pharmacology of obesity: benefits and risks.

The prevalence of obesity in Western countries has increased at a much greater pace than the development of new efficient and safe drugs, beyond mere lifestyle changes, for the treatment of overweight. Numerous different types of drugs which had been used in the past for the treatment of obesity have currently been withdrawn due to undesirable long-term side effects. The only available drug in Europe is orlistat, which serves only as an aid for the treatment of obesity. In the USA, however, a few central adrenergic-mediators, for instance, diethylpropion and phentermine, have been available for decades to treat obesity during a short-term period (less than 12 weeks). The Food and Drug Administration (FDA) has recently approved lorcaserin and the combination phentermine/ topiramate for the treatment of obesity. The first one is a selective serotonin 2C receptor agonist that works by decreasing food intake with few side effects. Its outcomes on weight are modest, but may be helpful in certain selected patients. The phentermine/topiramate combination has proved to be highly effective, achieving a 10% reduction in weight in the majority of patients, although attention must be drawn to the possible development of side effects in both the short and the long-term follow-up. Further investigation regarding the mechanisms involved in weight balance will anticipate the development of new expectations for the treatment of obesity in the near future.

El incremento de la prevalencia de obesidad en los países occidentales no ha sido paralela al desarrollo de nuevos fármacos eficaces y seguros a largo plazo para el tratamiento del exceso de peso más allá de los cambios en el estilo de vida. La larga lista de fármacos que se han utilizado para el tratamiento de la obesidad han tenido que ser retirados por efectos secundarios indeseables para la salud a largo plazo. En Europa solo contamos con orlistat, como único fármaco coadyuvante para el tratamiento de la obesidad, mientras que en EEUU hace décadas disponen de unos pocos fármacos adrenérgicos de acción central (como Dietilpropion o Phentermine) para un tratamiento a corto plazo (inferior a 12 semanas). Recientemen te, la Food and Drug Administration (FDA), acaba de aprobar la lorcaserina y la combinación de Phentermine y topiramate. Lorcaserine es un agonista específico del receptor serotoninérgico 2c, con actividad anorexígena y pocos efectos secundarios. Sus efectos sobre el peso son moderados, pero pueden ser de utilidad en algunos pacientes seleccionados. La combinación de phentermine y topiramate es muy eficaz alcanzando un 10% de pérdida de peso en una mayoría de pacientes, aunque debemos estar atentos acerca de sus potenciales efectos secundarios a corto y largo plazo. La profundización en la investigación de los mecanismos implicados en la regulación del peso corporal conllevará nuevas expectativas de tratamientos para la obesidad en un futuro próximo.

Update on pharmacology of obesity: Benefts and risks / Farmacología de la obesidad al día: beneficios y riesgos

The prevalence of obesity in Western countries has increased at a much greater pace than the development of new efficient and safe drugs, beyond mere lifestyle changes, for the treatment of overweight. Numerous different types of drugs which had been used in the past for the treatment of obesity have currently been withdrawn due to undesirable long-term side effects. The only available drug in Europe is or listat, which serves only as an aid for the treatment of obesity. In the USA, however, a few central adrenergic-mediators, for instance, diethylpropion and phentermine, have been available for decades to treat obesity during a short-term period (less than 12 weeks).The Food and Drug Administration (FDA) has recently approved lorcaser in and the combination phentermine/topiramate for the treatment of obesity. The first one is a selective serotonin 2C receptor agonist that works by decreasing food intake with few side effects. Its outcome son weight are modest, but may be helpful in certain selected patients. The phentermine/topiramate combination has proved to be highly effective, achieving a 10% reductionin weight in the majority of patients, although attention must be drawn to the possible development of side effects in both the short and the long-term follow-up. Further investigation regarding the mechanisms involved in weight balance will anticipate the development of new expectations for the treatment of obesity in the near future (AU)

El incremento de la prevalencia de obesidad en los países occidentales no ha sido paralela al desarrollo de nuevos fármacos eficaces y seguros a largo plazo para el tratamiento del exceso de peso más allá de los cambios en el estilo de vida. La larga lista de fármacos que se han utilizado para el tratamiento de la obesidad han tenido que ser retirados por efectos secundarios indeseables para la salud a largo plazo. En Europa solo contamos con orlistat, como único fármaco coadyuvante para el tratamiento de la obesidad, mientras que en EEUU hace décadas disponen de unos pocos fármacos adrenérgicos de acción central(como Dietilpropion o Phentermine) para un tratamiento acorto plazo (inferior a 12 semanas). Recientemente, la Food and Drug Administration (FDA), acaba de aprobarla lorcaserina y la combinación de Phentermine y topiramate. Lorcaserine es un agonista específico del receptor serotoninérgico 2c, con actividad anorexígena y pocos efectos secundarios. Sus efectos sobre el peso son moderados, pero pueden ser de utilidad en algunos pacientes seleccionados. La combinación de phentermine y topiramatees muy eficaz alcanzando un 10% de pérdida de peso en una mayoría de pacientes, aunque debemos estar atentos acerca de sus potenciales efectos secundarios acorto y largo plazo. La profundización en la investigación de los mecanismos implicados en la regulación del peso corporal conllevará nuevas expectativas de tratamientos para la obesidad en un futuro próximo (AU)

Tratamiento farmacológico de la obesidad / No disponible

No disponible

Complicaciones asociadas a la obesidad / No disponible

La obesidad constituye una patología crónica, que presentano solo una mayor mortalidad sino también comorbilidad,en relación a su gravedad (a mayor IMC mayores complicaciones)y a su distribución (mayores comorbilidades conobesidad central que con la de distribución periférica).Dentro de las comorbilidades mayores tenemos la diabetesmellitus tipo 2, el síndrome de hipoventilación-obesidad,el síndrome de apnea obstructiva del sueño, la hipertensiónarterial, la enfermedad cardiovascular, algunos tiposde neoplasias (endometrio, mama, hígado) y la artropatíadegenerativa de articulaciones de carga.Dentro de las comorbilidades menores caben destacar ladislipemia, el reflujo gastroesofágico, la colelitiasis, el hígadograso, la infertilidad, el síndrome de ovarios poliquísticos, laincontinencia urinaria, la nefrolitiasis, otros tipos de cáncer(esófago, colon-recto, próstata, vesícula biliar), la insuficienciavenosa, la fibrilación auricular, la insuficiencia cardiacacongestiva, ciertos tipos de demencias y la hipertensiónendocraneal benigna(AU)

The obesity is a chronic disease directly associated withhigh mortality and morbidity where the higher the BMIand the more central is the distribution the more risk forcomplications.Among the major complications of obesity are: type 2 Diabetes,obesity-hypoventilation syndrome, obstructive sleepapnea syndrome, Arterial Hypertension, cardiovasculardisease, certain types of malignancies (endometrial, breast,liver) and the osteoarthritis in weight bearing joints. TheMinor complications includes: the dyslipidemias, gastroesophagealreflux, gall bladder stones, fatty liver, infertility,polycystic ovarian syndrome, urinary incontinence, renal calculus,other types of malignancies (esophagus, recto-colon,prostate, gall bladder), venous insufficiency, atrial fibrillation,congestive heart failure, certain types of dementia and thebenign intracranial hypertension(AU)