title: Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients.
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.
authors.affiliation: Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: I B
authors.initials: IB
authors.lastname: Skottheim
authors.forename: K
authors.initials: K
authors.lastname: Stormark
authors.forename: H
authors.initials: H
authors.lastname: Christensen
authors.forename: G S
authors.initials: GS
authors.lastname: Jakobsen
authors.forename: J
authors.initials: J
authors.lastname: Hjelmesaeth
authors.forename: T
authors.initials: T
authors.lastname: Jenssen
authors.forename: J L E
authors.initials: JL
authors.lastname: Reubsaet
authors.forename: R
authors.initials: R
authors.lastname: Sandbu
authors.forename: A
authors.initials: A
authors.lastname: Asberg
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000143:Acids / Q000378:metabolism; D000328:Adult; D019540:Area Under Curve; D000069059:Atorvastatin; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D015390:Gastric Bypass; D005838:Genotype; D006538:Heptanoic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*; D007783:Lactones / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism* / Q000601:surgery*; D011446:Prospective Studies; D011758:Pyrroles / Q000737:chemistry / Q000493:pharmacokinetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000143:Acids; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; D011758:Pyrroles; D004247:DNA; D000069059:Atorvastatin; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A