Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients.
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.
Skottheim
I B
IB
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
Stormark
K
K
Christensen
H
H
Jakobsen
G S
GS
Hjelmesaeth
J
J
Jenssen
T
T
Reubsaet
J L E
JL
Sandbu
R
R
Asberg
A
A
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
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