Significant Increase in Systemic Exposure of Atorvastatin After Biliopancreatic Diversion With Duodenal Switch

Abstract

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.

Vitamin, Mineral, and Drug Absorption Following Bariatric Surgery

“…[124,125] Their studies were based on the recognition of inter-individual variability of enzymatic expression and consequently, differences in first-pass metabolism as a potential effect in drug bioavailability. From 12 morbidly obese patients undergoing gastric bypass, and 10 patients undergoing BPD/DS, pharmacokinetic measurements were obtained as well as genotypic profiling for CYP3AC and ABCB1.…”

“…Those patients with the lowest systemic exposure (high enzymatic expression) prior to surgery showed a median 1.2-fold increase in AUC of the drug (range of 0.8–2.3, P =0.03) and a 2-fold increase after BPD (range 1.0–4.2, P = 0.001). [124,125] Since CYP enzymatic content is greater in the proximal portions of the small intestine, bypass of this segment should cause an important reduction in intestinal metabolic activity. Therefore, this may increase the bioavailability of certain drugs as in this case atorvastatin.…”

Effect of a Roux-en-Y Gastric Bypass on the Pharmacokinetics of Oral Morphine Using a Population Approach

“…Only one compared drug pharmacokinetics at different times after RYGB [6]. It has been difficult to draw any general conclusion; the effects of some oral drugs remain unchanged or are increased (atorvastatin, moxifloxacin, metformin), while those of others are reduced (selective serotonin reuptake inhibitors), according to the post operative period [3][4][5][6][7][8][9][10]. It is therefore necessary to carry out controlled studies on each specific drug of interest to evaluate the specific effect of obesity and of RYGB on the pharmacokinetics of that particular drug.…”

“…Clinical studies performed recently have involved a small number of patients or were control-case studies [3][4][5][6][7][8][9][10]. Only one compared drug pharmacokinetics at different times after RYGB [6].…”

Pharmacokinetic Changes Secondary to Roux en Y Gastric Bypass

“…The effects of RYGB on the pharmacokinetic parameters of atorvastatin were investigated in 12 patients (66% female, mean age 52 years) who were going to undergo RYGB [31]. Subjects who were scheduled for RYGB were eligible for the study if they were being treated with atorvastatin 20-80 mg daily (mean dose 37 mg daily).…”