Jan Peter Yska

Remission of Type 2 Diabetes Mellitus in Patients After Different Types of Bariatric Surgery: A Population-Based Cohort Study in the United Kingdom.

IMPORTANCE To our knowledge, an observational study on the remission of type 2 diabetes mellitus (T2DM) after different types of bariatric surgery based on data from general practice has not been carried out. OBJECTIVE To assess the effect of different types of bariatric surgery in patients with T2DM on diabetes remission compared with matched control patients, and the effect of the type of bariatric surgery on improvement of glycemic control and related clinical parameters. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study conducted from May 2013 to May 2014 within the Clinical Practice Research Datalink involving 2978 patients with a record of bariatric surgery (2005-2012) and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or greater. We identified 569 patients with T2DM and matched them to 1881 patients with diabetes without bariatric surgery. Data on the use of medication and laboratory results were evaluated. EXPOSURES Bariatric surgery, stratified by type of surgery (gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy, or other/unknown). MAIN OUTCOMES AND MEASURES Remission of T2DM (complete discontinuation of glycemic therapy, accompanied with a subsequently recorded hemoglobin A1c level<6.0%). RESULTS Among patients undergoing bariatric surgery, we found a prevalence of 19.1% for T2DM. Per 1000 person-years, 94.5 diabetes mellitus remissions were found in patients who underwent bariatric surgery compared with 4.9 diabetes mellitus remissions in matched control patients. Patients with diabetes who underwent bariatric surgery had an 18-fold increased chance for T2DM remission (adjusted relative rate [RR], 17.8; 95% CI, 11.2-28.4) compared with matched control patients. The greatest effect size was observed for gastric bypass (adjusted RR, 43.1; 95% CI, 19.7-94.5), followed by sleeve gastrectomy (adjusted RR, 16.6; 95% CI, 4.7-58.4) and gastric banding (adjusted RR, 6.9; 95% CI, 3.1-15.2). Body mass index and triglyceride, blood glucose, and hemoglobin A1c levels sharply decreased during the first 2 years after bariatric surgery. CONCLUSIONS AND RELEVANCE Population-based data show that bariatric surgery strongly increases the chance for remission of T2DM. Gastric bypass and sleeve gastrectomy have a greater effect than gastric banding. Although the risks and possible adverse effects of surgery should be weighed against its benefits, bariatric surgery and, in particular, gastric bypass or sleeve gastrectomy may be considered as new treatment options for T2DM.

Influence of Bariatric Surgery on the Use and Pharmacokinetics of Some Major Drug Classes

The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes. Very few studies have been published on the influence of bariatric surgery on the pharmacokinetics of drugs. After bariatric surgery, theoretically, reduced drug absorption may occur. Correct dosing and choosing the right dosage form for drugs used by patients after bariatric surgery are necessary for optimal pharmacotherapy. Therefore, more clinical studies are needed on the influence of bariatric surgery on the pharmacokinetics of major drugs.

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.

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

Objective Medication errors in ambulatory care are frequent. Because the process of prescribing and medication therapy is more complex than in hospital settings adequate methods to avoid medication errors are difficult to implement. In our study we investigated a campaign from a health insurance company that had the aim to increase medication safety within insurants with polypharmacy and multimorbidity. Method An expert team consisting of clinical pharmacologists and a pharmacist analysed the medication of insurants for risk prescriptions who had an additional telephonic health coaching. Attending physicians received a report and were offered to contact the experts for counselling. Results of medication analyses of 400 insurants were categorized in eight types of prescribing errors and feedback from the physicians was recorded. Differences in medication therapy after counselling were scanned. Main outcome measure The frequency of medication errors in eight categories and physicians’ feedback, further changes in medications of physicians responding. Results Insurants were 48% female and 52% male and took an average of 13.4 drugs regularly. 16.8% of the physicians contacted replied, 13.3% had a counselling conversation. 29.2% of the physicians replying gave a positive response to the campaign, 13.8 % a negative and for 56.9 % a neutral feedback was given. Out of a total of n=2524 errors 26.8% occurred in the category missing indication, 6.8% in PRISCUS medication, 33.3% in interactions, 15.3% in wrong dosage, 0.9% in contraindication, 2.8% in dosage adaption to renal function, 6.9% in double medication and 7.2% in gap of prescribing. Conclusion A large number of medication errors appear in ambulatory care and consequently adverse drug events and hospital admissions are more likely to happen. Medication check by pharmacotherapy experts and pharmacological consulting with a high response of physicians can be a key tool to reduce these errors. Cooperation of a health insurance company and clinical pharmacologists is an effective association but needs to be optimized for better acceptance and more rapid ability to react.

A GASTROINTESTINAL SIMULATION SYSTEM (GISS) FOR DISSOLUTION OF DRUGS BEFORE AND AFTER ROUX-EN-Y GASTRIC BYPASS: FIRST RESULTS

S OF THE DUTCH SOCIETY OF CLINICAL PHARMACOLOGY AND BIOPHARMACY MEETING OF MARCH 26, 2013 DOPAMINE D2 AGONIST INDUCED CARDIOVASCULAR CHANGES IN YOUNG HEALTHY MEN. A PHASE I CLINICAL TRIAL EXPERIENCE K Abou Farha, S van Os, C Balje & W Tamminga QPS B.V, the Netherlands and Synthon BV, the Netherlands Introduction Dopamine D2 (DA2) agonists are a first line treatment option in young Parkinson’s patients with mild to moderate symptoms. DA2 agonists are known to cause depression of cardiac functions with decrease in heart rate. A recent European multicentre study [1] found a relationship between the use of DA2 agonists in Parkinson’s disease (PD) and heart failure (HF) especially in early phase of therapy. Results Here we present data of a Phase I study where we evaluated supine (SU) and standing (ST) blood pressure (BP) and brachial pulse rate (PR) levels, obtained from 40 healthy male volunteers, aged 18–55 year, after administration of a selective DA2 agonist. Full medical screening indicated the healthy status of all participants. The DA2 agonist was administered in an escalating dose level design over 30 days, 13 up-titration (UPT) days; 12 steady state (SS) days, and 5 down titration days. An oral dose of 10 mg domperidone tid was given to prevent potential D2 cardiovascular and gastrointestinal peripheral effects. Data were categorised into 2 age groups,G1 (18–40 years) and G2 (40–55 years). Statistical comparison between BP and brachial PR obtained in SU and ST positions during screening (BL), UPT phase and SS period revealed significant results (Table 1). All 40 subjects showed an increase in both SU and resting ST PR as compared to base line (with a zenith of 239 bpm in resting ST position vs. 60 bpm (BL). Increased SU Systolic (S)BP was observed in 36 subjects (26 G1 and 10 G2) with a zenith of 175 mmHg in 1 subject vs.138 mmHg). Increased ST SBP was observed in 33 subjects (24 G1 and 9 G2) with a zenith of 202 mmHg in 1 subject vs. 125 mmHg at BL. Seven of the 28 G1 subjects were removed prematurely from the trial because of clinically significant symptomatic increase in BP (up to 202/95 mmHg, ca. 81 mmHg and 20 mmHg increase respectively in SBP and DPB above BL) and tachycardia of 151 bpm, obtained from a 12leads ECG. In 3 of the 7 subjects non-specific ST-segment depression was seen in the inferior limb leads of concurrently obtained ECG (Figure 1). The clinical condition implied immediate administration of I.V. rescue medications including a selective β-1 blocker in all 7 subjects. In 1 subject with an inadequate response an I.V. α-β-1 blocking agent was added to therapy. Table 1 Systolic blood pressure (SBP) and brachial pulse rate (PR) for group 1 (18–40 years) and group 2 (40–55 years) in supine and standing position during screening (BL), UPT and SS phase Parameter Supine Standing