1. ¹Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
2. ²Morbid Obesity Center, Vestfold Hospital Trust, Tønsberg, Norway
3. ³Medical Department, Rikshospitalet Medical Centre, University of Oslo, Oslo, Norway
4. ⁴Medical Department, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway

Correspondence: R Sandbu, (rune.sandbu@siv.no)

Received 4 March 2009; Accepted 19 April 2009; Published online 3 June 2009.

Abstract

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.