Exploring optimal pharmacotherapy after bariatric surgery: where two worlds meet

In dit proefschrift staan diverse aspecten van de optimale toepassing van geneesmiddelen na overgewichtschirurgie (bariatrische chirurgie) centraal. Door de veranderingen in het maagdarmkanaal na een operatie, kunnen de effectiviteit en de veiligheid van geneesmiddelen veranderen. Over de effectieve en veilige toepassing van geneesmiddelen na een bariatrische ingreep is nog vrij weinig bekend. Specifiek richten de onderzoeken in het proefschrift zich op de volgende onderwerpen. Metoprolol is een geneesmiddel dat veel wordt toegepast bij hoge bloeddruk en hart- en vaatziekten. Een onderzoek met vrouwelijke patiënten toonde aan, dat de biologische beschikbaarheid van metoprolol tabletten kan worden beïnvloed door een bepaald type bariatrische ingreep (Roux-en Y gastric bypass). Patiënten die na deze ingreep metoprolol gebruiken, dienen nauwgezet in de gaten te worden gehouden met mogelijk aanpassing van de dosering. Ondanks richtlijnen om het gebruik van NSAID’s (een soort pijnstillers) na de operatie te vermijden is het gebruik bij patiënten die bariatrische chirurgie hebben ondergaan, aanzienlijk. Een interventiestudie gericht op het verminderen van het gebruik van NSAID’s was niet succesvol. Een risicosituatie blijft daarmee bestaan en vraagt vervolgonderzoek. Op basis van onderzoek met een uitgebreide database van Britse huisartsen hebben wij aangetoond, dat bariatrische chirurgie de kans op remissie van type 2 diabetes mellitus sterk verhoogt. Een bariatrische operatie, met name een gastric bypass of sleeve operatie, kan als nieuwe behandeling voor type 2 diabetes mellitus worden overwogen. Kennis van de soorten bariatrische operaties en hun mogelijke invloed op het gebruik en de biologische beschikbaarheid van geneesmiddelen, is een voorwaarde voor optimale medicatiebewaking

Long-term Effect of Bariatric Surgery on the Use of Levothyroxine and Thyroid Levels

BACKGROUND: The aim of this study was to evaluate the effect of bariatric surgery on the defined daily dose of levothyroxine (DDD LT4), thyroid-stimulating hormone (TSH), and free thyroxine (fT4) in female patients with hypothyroidism until 48 months after surgery. METHODS: A retrospective observational study of hypothyroid patients who underwent bariatric surgery. Changes in DDD LT4, TSH, and fT4 over a 48 month period after surgery were analyzed. RESULTS: Thirty-seven patients were included: 27 Roux-en-Y gastric bypass (RYGB), 6 sleeve gastrectomy (SG), 3 adjustable gastric band, and 1 one anastomosis gastric bypass. The median DDD LT4 decreased from 125 µg at baseline to 100 µg 12 months after surgery. From 24 to 48 months after surgery, the median DDD LT4 was stable at 125 µg. Most dose adjustments occurred during the first 24 months after surgery. In the time period of 24-48 months after surgery, the dose remained stable in 73.1% of the RYGB patients and in 60.0% of the SG patients. After 48 months in the RYGB group, no significant change in TSH and fT4 levels was observed. CONCLUSIONS: Bariatric surgery led to frequent dose adjustments during the first 2 years after surgery. However, 24-48 months after surgery in the majority of patients, the dosage remained stable. No significant change in TSH and fT4 was observed 48 months after RYGB. In the first 2 years after surgery, clinicians should frequently monitor TSH and fT4 for individual dose adjustment of levothyroxine. Thereafter, the frequency of monitoring may be decreased

Manufacturing study medication for clinical trials

Regulations applicable to the manufacture of study medication are dependent on the extent of involvement of the hospital pharmacy in the process

Talismans et amulettes chinois

International audienc

NSAID Use after Bariatric Surgery: a Randomized Controlled Intervention Study

Background Use of nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in bariatric surgery patients. If use of an NSAID is inevitable, a proton pump inhibitor (PPI) should also be used. Aim To determine the effect of an, compared to care-as-usual, additional intervention to reduce NSAID use in patients who underwent bariatric surgery, and to determine the use of PPIs in patients who use NSAIDs after bariatric surgery. Methods A randomized controlled intervention study in patients after bariatric surgery. Patients were randomized to an intervention or a control group. The intervention consisted of sending a letter to patients and their general practitioners on the risks of use of NSAIDs after bariatric surgery and the importance of avoiding NSAID use. The control group received care-as-usual. Dispensing data of NSAIDs and PPIs were collected from patients' pharmacies: from a period of 6 months before and from 3 until 9 months after the intervention. Results Two hundred forty-eight patients were included (intervention group: 124; control group: 124). The number of users of NSAIDs decreased from 22 to 18 % in the intervention group and increased from 20 to 21 % in the control group (NS). The use of a PPI with an NSAID rose from 52 to 55% in the intervention group, and from 52 to 69 % in the control group (NS). Conclusions Informing patients and their general practitioners by letter, in addition to care-as-usual, is not an effective intervention to reduce the use of NSAIDs after bariatric surgery (trial number NTR3665)

Influence of bariatric surgery on the use of some major drug classes

Introduction Patients undergoing bariatric surgery are severely obese and characterized by multidrug use for multiple comorbidities. Bariatric surgery can influence the prevalence and incidence of comorbidities, as well as the pharmacokinetics of drugs. This might lead to changes in the use of drugs. Aim To study the influence of bariatric surgery on the use of medication in patients before and after surgery, focusing on type and number of medications and daily dosage. Methods A retrospective and prospective observational study was carried out in Medical Centre Leeuwarden. After having obtained written informed consent drug dispensing data from pharmacies were collected from patients undergoing their first bariatric surgery between January 2008 and September 2011. Dispensing data from 6 months before until 12 months after surgery were analyzed. Drugs were classified according to the WHO-ATC classification system. Dosages of drugs were compared using defined daily dose (DDD). Results 450 patients were included (20.2% male). Mean age (SD) was 43.4 (10.1) yr; mean BMI (SD) was 44.9 (6.7) kg/m2. Roux-en-Y gastric bypass was performed in 74% of the patients. Mean BMI (SD) 12 months after surgery was 31.1 (5.6) kg/m2. The mean number of drugs per patient (95% CI) decreased from 3.66 (3.37-3.99) to 3.25 (3.04- 3.56). The mean number of drugs per patient decreased by 71%, 36%, 27%, 47%, 24% and 33% for antidiabetics, diuretics, beta blockers, agents acting on the reninangiotensin system, lipid modifying agents, and drugs for obstructed airway diseases respectively 12 months after surgery. From those drug classes patients used lower DDD 12 months after surgery. In contrast, a higher DDD was observed for thyroid hormone with no change in the mean number of drugs per patient. Conclusion Twelve months after bariatric surgery the use of drugs decreases in terms of mean number of drugs per patient and, for some major drug classes, in dose intensity. Dispensing data from pharmacies may provide detailed information on the use of medication by patients after bariatric surgery

A gastrointestinal simulation system for dissolution of oral solid dosage forms before and after Roux-en-Y gastric bypass

Background: The Roux-en-Y gastric bypass (RYGB) is a bariatric procedure, greatly reducing the stomach size and bypassing the duodenum and proximal jejunum. Hence, RYGB may reduce the absorption and bioavailability of oral medication. For clinical decisions on the use of medication, knowledge of altered modifications in drug disposition is a prerequisite. An in vitro dissolution method for solid oral medications, simulating conditions before and after RYGB, might be a valuable tool to predict the pharmaceutical availability of medicines frequently used by patients after RYGB. Objectives: To develop a gastrointestinal simulation system (GISS), mimicking conditions before and after RYGB for investigating dissolution characteristics of solid oral medications, and to assess the pharmaceutical availability of metoprolol from immediate-release (IR) and controlled-release (CR) tablets under these conditions. Methods: With an adjusted, pharmacopoeial paddle dissolution apparatus, the GISS enables variation in parameters which are relevant to drug release in vivo: pH, volume, residence time, osmolality and agitation. Metoprolol tartrate 100 mg IR tablets and metoprolol CR tablets were tested. Release profiles were determined by measuring the concentrations of metoprolol spectrophotometrically. Results: From IR tablets, under all conditions applied, >85% of metoprolol was released within 25 min. From all tested CR tablets >90% of metoprolol was released after 22 hours. Conclusions: This GISS is a suitable dissolution system to assess pharmaceutical availability before and after RYGB. In patients who have undergone RYGB, no problems in pharmaceutical availability of metoprolol IR and CR tablets are to be expected. Any changes in response to metoprolol in patients after RYGB should therefore be ascribed to changes in bioavailability