Among patients with severe obesity followed up for a median of 6.5 years, bariatric surgery compared with medical treatment was associated with a clinically important increased risk for complications, as well as lower risks of obesity-related comorbidities. The risk for complications should be considered in the decision-making process.

The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obese patients being treated with 20-80 mg atorvastatin each morning. Eight-hour pharmacokinetic investigations were performed the day before the surgery and at a median of 5 weeks (range 3-6 weeks) after the surgery. Gastric bypass surgery produced a variable effect on individual systemic exposure to atorvastatin acid (area under the plasma concentration vs. time curve from 0 to 8 h postdose (AUC(0-8))), ranging from a threefold decrease to a twofold increase (median ratio = 1.1, P = 0.99). Patients with the highest systemic exposure to atorvastatin before surgery showed reduced exposure after surgery (n = 3, median ratio = 0.4, range = 0.3-0.5, P < 0.01), whereas those with lower systemic exposure before surgery showed a median 1.2-fold increase in atorvastatin AUC(0-8) (n = 9, range = 0.8-2.3, P = 0.03) after surgery. This study indicates that the presurgical first-pass metabolic capacity influences the effect of gastric bypass on atorvastatin bioavailability. Because individual first-pass metabolic capacity is not readily assessable clinically, retitration up to the lowest effective dose should be performed after the surgery.

Individual variability in expression and function of organic anion-transporting polypeptide 1B1 (OATP1B1), multidrug resistance protein 1 (MDR1), and/or cytochrome P450 3A4 (CYP3A4) may impact the clinical response of many drugs. We investigated the correlation between expression of these proteins and pharmacokinetics of atorvastatin, a substrate of all three, in 21 obese patients with paired biopsies from liver and intestinal segments. The patients were also screened for the SLCO1B1 c.521T→C variant alleles. Approximately 30% (r(2) = 0.28) of the variation in oral clearance (CL/F) of atorvastatin was explained by hepatic OATP1B1 protein expression (P = 0.041). Patients carrying the SLCO1B1 c.521C variant allele (homozygous, n = 4; heterozygous, n = 2) exhibited 45% lower CL/F of atorvastatin than the c.521TT carriers (P = 0.067). No association between hepatic and intestinal expression of MDR1 or CYP3A4 and atorvastatin pharmacokinetics was found (P > 0.149). In conclusion, this study suggests that OATP1B1 phenotype is more important than CYP3A4 and MDR1 phenotypes for the individual pharmacokinetic variability of atorvastatin.

Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure. Given that this procedure introduces a bypass of the proximal small intestine, it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability. Eight-hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at (median) 6 weeks (range, 4-8 weeks) in 10 morbidly obese patients who were receiving treatment with 20-80 mg atorvastatin each morning. The bioavailability of atorvastatin acid was significantly increased, with a mean twofold higher AUC(0-8) after surgery (range 1.0-4.2, P = 0.001). Time to maximum plasma concentration (C(max)) increased from 1.2 h before surgery to 2.3 h after surgery (P = 0.03). The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds. Consequently, retitration to the lowest effective dose should be considered after biliopancreatic diversion with duodenal switch in the case of drugs with a high degree of intestinal first pass metabolism and a narrow therapeutic window.

This study confirms that nonantibiotic management of acute uncomplicated diverticulitis is safe and feasible. Most complications occurred in a small group of high-risk patients treated with antibiotics.

BackgroundA previous study of 22 patients undergoing either gastric bypass or duodenal switch showed increased systemic exposure of atorvastatin acid 3–8 weeks after surgery in the majority of patients. This study aimed to investigate the long-term effects on systemic exposure of atorvastatin acid in the same group of patients.MethodsAn 8-h pharmacokinetic investigation was performed a median of 27 months (range 21–45 months) after surgery. Systemic exposure was measured as the area under the plasma concentration versus the time curve from 0 to 8 h postdose (AUC0–8). Linear mixed models with AUC0–8 as the dependent variable were implemented to assess the effect of time, surgical procedure, and body mass index (BMI) as explanatory variables.ResultsThe study enrolled 20 patients. The systemic exposure of atorvastatin acid changed significantly over time (p = 0.001), albeit there was substantial variation between subjects. The effect of time was attenuated but remained significant after adjustment for surgical procedure and BMI (p = 0.048). The initial AUC0–8 increase seen in the majority of patients 3–8 weeks after surgery was normalized long term, with 7 of the 12 gastric bypass patients and 6 of the 8 duodenal switch patients showing decreased AUC0–8 compared with preoperative values.ConclusionsThe systemic exposure of atorvastatin showed a significant change over time after bariatric surgery, albeit with large inter- and intraindividual variations. The findings indicate that patients using atorvastatin or drugs with similar pharmacokinetic properties should be monitored closely for both therapeutic effects and adverse events the first years after gastric bypass and duodenal switch. ClinicalTrial NCT00331565.

BackgroundBariatric surgery particularly benefits patients with obesity-related comorbidities such as type 2 diabetes and obstructive sleep apnea. We aimed to examine whether the variables that influence treatment choice differ between morbidly obese patients undergoing bariatric surgery and those opting for conservative treatments.MethodsA total of 505 consecutive morbidly obese patients (72% women; mean (SD) age 42 (12) years) who attended our tertiary care center between December 2005 and February 2007 were examined by a multidisciplinary team and offered surgical or conservative treatment. The chi-square test, independent samples t test, and multiple logistic regression were used in the statistical analyses.ResultsA total of 249 (49%) patients underwent bariatric surgery. When compared to the conservative group of patients, the surgery group was characterized by a significantly higher mean (SD) BMI (46.5(6.2) vs. 43.2(5.5) kg/m2, p < 0.001), earlier onset of obesity (40% vs. 26% before 12 years of age, p < 0.001), and lower age (41(11) vs. 44(13) years, p = 0.002). In contrast, the groups did not differ significantly with respect to gender or obesity-related comorbidities. After adjustments for gender, age, onset of obesity, and the number of comorbidities, multiple regression revealed that patients with BMI 40–50 or >50 kg/m2 had between 3 (OR = 3.0; 95% CI 1.9–4.9, p < 0.001) and 6 (OR = 5.7; 95% CI 3.0–11.0, p < 0.001) times the chance of undergoing bariatric surgery when compared to patients with a BMI <40 kg/m2 (reference).ConclusionOur data indicates that increasing BMI rather than obesity-related comorbidities, predicted treatment choice in morbidly obese patients.

Complications after bariatric surgery may manifest in the long term. Regular follow-up is required. General practitioners should be responsible for follow-up in the long term, and should be familiar with common and serious complications as well as normal symptomatology after bariatric surgery.