Frequently Asked Questions
How is drug absorption altered by bariatric surgery
Introduction
With more than 30 million Americans considered clinically obese, obesity has become a very serious he
contributes to approximately 6% of all health care expenditures.1 Aside from its financial impact, obesity
of as many as 300,000 patients annually. The prevalence of obesity has greatly increased over the past
related health effects, continues to grow.2 Obesity is associated with an increased risk for the developm
cardiovascular disorders, and leads to poorer outcomes of co-morbid disease states. Due to the fact tha
United States is obese, it may become more common for pharmacists to interact with morbidly obese pa
procedure to facilitate weight loss. Although the number of bariatric surgical procedures performed cont
addressing drug absorption and other medication concerns remains limited. It is essential that pharmaci
order to guide medication therapy in this patient population.
Treatment of obesity
Approaches to weight management include diet, exercise, behavior modification, pharmacologic therapy
treatment options may reduce weight, they do so at a modest rate of 2% to 10% after 1 year.3 Surgery is
for obesity. However, since surgical procedures come with their own set of risks, this option is usually re
defined as having a body mass index (BMI) > 40 kg/m2 or a BMI > 35 kg/m2 with comorbidity.2 Approxim
surgery in the United States in 2008.4 This number is only expected to rise in the upcoming years. Surge
stomach volume. However, by doing so, this causes a reduction in gastrointestinal (GI) surface area, wh
alteration of the GI tract that occurs with bariatric surgery is likely to alter not only the absorption of vitam
orally administered medications. As pharmacists, we rely on normal conditions for drug absorption; how
drugs warrant special consideration.
Types of bariatric surgical techniques
Bariatric surgery can be described as surgical procedure that aims to limit caloric intake, decrease nutrie
major types of bariatric surgery being used in the United States for the management of obesity.1 These
gastroplasty, adjustable gastric banding, and conventional Roux-en-Y gastric bypass. Each of these pro
malabsorption, restricting gastric volume, or a combination of these mechanisms.4 Each procedure com
as unique drug administration concerns.
Vertical-banded gastroplasty and adjustable gastric banding utilize restrictive (reduction of caloric intake
vertical-banded gastroplasty, a portion of the stomach is stapled to form a small pouch, reducing stomac
now usually done laparoscopically, involves inserting a silicone band lined with an inflatable balloon aro
cm below the gastroesophageal junction.4 This creates a 30-mL upper gastric pouch, which limits food in
controlled by adjusting the level of balloon inflation. This procedure is purely restrictive and thus, reduce
procedures were historically performed in the United States; however, while they result in fewer postope
replaced by combination restrictive and malabsorptive (reduction of the absorptive capacity of the intest
The Roux-en-Y gastric bypass is most commonly performed in the United States and produces a more
other two methods.2,5 This procedure uses a combined restrictive and malabsorptive approach to induce
mL portion of the stomach is sectioned off in an effort to limit food intake. The small intestine is then cut
intestine is connected to the pouch at the top of the stomach. The narrow opening to the small intestine
a sensation of early satiety.6 By circumventing the lower portion of the stomach (90% to 95%) and much
part of the proximal jejunum), the surface area for absorption is greatly decreased and malabsorption ca
Drug absorption and bariatric surgery
The mechanism of altered drug absorption depends partly on the type of procedure done-restrictive or m
affected by drug disintegration and solubility and the surface area available for absorption, all of which c
Disintegration of the dosage form is the first step needed for drug absorption. The smaller volume of the
adequate tablet or capsule disintegration due to reduced gastric mixing.7 Solubility of a drug is depende
pH are absorbed in the stomach, while those that are soluble in more basic environments are absorbed
volume after bariatric surgery result in a decrease in gastric acid production and a higher pH compared
may cause a decrease in the absorption of medications that rely on an acidic pH for solubility or absorpt
stomach may further decrease drug bioavailability. These changes may be especially important for drug
release formulations. Use of liquid formulations or chewing or crushing solid dosage forms (if appropriat
Malabsorptive procedures bypass much of the small intestine.7 This technique not only decreases intes
drugs and alters intestinal transit time. Mixing of highly lipid soluble drugs with bile acids may be reduce
decreased absorption.
In addition to drug absorption, drug distribution can also be affected following bariatric surgery.8 Obesity
distribution include increased blood volume, cardiac output, lean body mass, organ size, and adipose m
expected to change and, therefore, may necessitate drug dosing adjustments.
Literature Summary
Management of medications after bariatric surgery presents unique challenges and is often only guided
surgery on drug absorption has not been widely investigated.4 The quality of data are often poor and pu
bariatric surgery is usually limited to case reports and data from small studies. In addition, data from old
techniques and procedures that are no longer in use. Table 1 summarizes recent case reports describin
surgery.
Table 1. Reports of Alterations in Drug Absorption Following Bariatric Surgery.
Drug/usual absorption Bariatric procedure Study description
and oral bioavailability
O
Antibiotics
Amoxicillin9


Well absorbed; exact
site of absorption not
specified10
89% oral
bioavailability12
Amoxicillin/clavulanate9


Well absorbed; exact
site of absorption not
specified10
Oral bioavailability
unknown
Nitrofurantoin9


Absorbed in proximal
small intestine
87% oral
bioavailability10
Antineoplastic agents
Roux-en-Y gastric
bypass
Case report: 29-year-old
pregnant female with history
of bariatric surgery for morbid
obesity given oral antibiotics
a urinary tract infection.
Despite sensitivity and
compliance with 3 different
regimens (amoxicillin,
nitrofurantoin, and
amoxicillin/clavulanate),
infection progressed to
pyelonephritis.
Th
tre
fo
W
w
Imatinib11


Likely absorbed in
stomach proximal
duodenum
98% oral
bioavailability
Sleeve gastrectomya Case report: 36-year-old
obese female with chronic
myeloid leukemia who
received imatinib 400 mg/day
for 4 years prior to sleeve
gastrectomy. Plasma imatinib
concentrations were measure
before and on 4 occasions
after the procedure.
M
co
40
va
65
62
da
H
co
ye
Th
se
un
su
im
Tamoxifen12



Case series: 3 female
patients with a history of
bariatric surgery, treated with
tamoxifen 20 mg/day for
breast cancer. All patients
had been taking tamoxifen for
at least 3 months.
Serum tamoxifen
concentrations were
measured to assess
absorption.
In
co
th
(th
m
re
di
Fo
52
20
se
(th
ng
Roux-en-Y gastric
bypass
Case report: 52-year-old male
diagnosed with glioblastoma
multiforme 3 months after
gastric bypass. After a
craniotomy, temozolomide
was given at 75 mg/m2 with
radiation, followed by a cycle
of temolozomide
monotherapy. Examination
for persistent symptoms
revealed tumor progression,
and a second surgery was
performed.
P
se
te
to
lit
Th
te
ad
su
Laparoscopic Rouxen-Y gastric bypass
Prospective, nonrandomized
pharmacokinetic study: 12
morbidly obese patients
treated with atorvastatin
S
(A
po
pa
Well absorbed from
the GI tract; exact site
of absorption not
specified10
Oral bioavailability
unknown
Temozolomide13

Roux-en-Y gastric
bypass
Exact site of
absorption not
specified
100% oral
bioavailability
Cardiovascular agents
Atorvastatin14

Absorbed in the
proximal small

intestine and
metabolized by CYP
enzymes in the small
intestine
14% oral
bioavailability15
before and after gastric
bypass.
de
ba
Th
re
su
ef
Immunosuppressive agents
Mycophenolic acid6


Roux-en-Y gastric
bypass
Rapidly absorbed;
exact site of
absorption not
specified16
94% oral
bioavailability18
Pharmacokinetic study: 4
C
dialysis and 2 renal transplant al
recipients
pa
co
Th
m
of
ad
im
Sirolimus6


Majority of absorption
occurs in proximal
duodenum
27% oral
bioavailability17
Tacrolimus6


Majority of absorption
occurs in proximal
duodenum
14% to 32% oral
bioavailability18
Antithrombotic agents
Warfarin19


Complete
gastrectomy and
Roux-en-Y
Absorbed from
stomach and proximal esophagojejunostomy
duodenum
100% oral
bioavailability20
a Procedure
Case report: 71-year-old
female with history of chronic
atrial fibrillation with stable
INR prior to surgery, requiring
5 to 6 mg/day.
After surgery, patient
experienced resistance to
warfarin, requiring up to 20
mg/day in order to reach
therapeutic INR.
A
w
tit
la
pu
on
w
IN
fo
where a portion of the stomach is removed surgically. Abbreviations: AUC, area under
CYP, cytochrome; GI, gastrointestinal; INR, international normalized ratio; IV, intravenous; T max, tim
In addition to the case reports described in Table 1, Padwal and colleagues published a systematic revi
surgery.7 The authors identified 15 case reports and 11 controlled trials describing the effects of bariatric
reports, evidence supporting decreased absorption was found for phenytoin, ethosuximide, rifampin, am
and thyroxine. In general dose increases were needed, due to low serum concentrations of the drug. It i
decreases in the drug dose after reversal of the bariatric procedure.
Seaman and colleagues conducted an in vitro study to assess changes in the dissolution of various psy
anxiolytics, and antipsychotics.21 The post-bypass test environment had a pH of 6.8 and was compared
pH). Of 22 medications tested, 12 had different dissolution characteristics in the 2 environments. Dissolu
compared with the control environment for amitriptyline, fluoxetine, paroxetine, sertraline, clonazepam, c
and ziprasidone. Two medications-bupropion and lithium carbonate-had better dissolution in the test en
noted two limitations to the trial: bioavailability was not studied and the tablets for the post-bypass enviro
done for patients following bariatric surgery.
Conclusion
Many patients are able to discontinue medications for chronic conditions, such as diabetes and hyperten
therapy is often needed for conditions unrelated to or not improved by weight loss. To better manage th
changes in the anatomy and physiology of the GI tract following bariatric surgery. Consider crushing all
release formulations to immediate-release dosage forms, when appropriate. Alternative dosage formula
will circumvent the need for tablet or capsule dissolution should also be considered. Ultimately, frequent
implemented in order to ensure correct dosing and to minimize side effects.
References
1. Jacobs D and Robinson M. Morbid obesity and operations for morbid obesity. In: Zinner MJ and Ashl
11th ed. http://www.accesssurgery.com/content. aspx?aID=128173.
2. St. Peter J and Billington C. Obesity. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey
approach. 7th ed. New York, NY: Mc-Graw-Hill; 2008:2437-2453.
3. Salameh B, Khoukaz M, Bell R. Metabolic and nutritional changes after bariatric surgery. Expert Rev
4. Chan L. Drug therapy-related issues in patients who received bariatric surgery (part I). Pract Gastroe
5. Miller A and Smith K. Medication and nutrient administration considerations after bariatric surgery. Am
6. Rogers C. Alloway R, Alexander J, Cardi M, Trofe J, Vinks A. Pharmacokinetics of mycophenolic acid
surgery in end-stage renal disease and transplant patients: a pilot study. Clin Transplant. 2008;22(3):28
7. Padwal R, Brocks D, Sharma A. A systematic review of drug absorption following bariatric surgery an
2010;11(1):41-50.
8. Macgregor A and Boggs L. Drug distribution in obesity and following bariatric surgery: A literature rev
9. Magee S, Shih G, Hume A. Malabsorption of oral antibiotics in pregnancy after gastric bypass surger
10. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (H
11. Pavlovsky C, Egorin M, Shah D, Beumer J, Rogel S, Pavlovsky S. Imatinib mesylate pharmacokinet
morbidly obese patients with chronic myeloid leukemia. Pharmacotherapy. 2009;29(9):1152-1156.
12. Wills S, Zekman R, Bestul D, Kuwajerwala N, Decker D. Tamoxifen malabsorption after Roux-en-Y
the literature. Pharmacotherapy. 2010;30(2):86e-90e.
13. Park D, Shah D, Egorin M, Beumer J. Disposition of temozolomide in a patient with glioblastoma mu
Neurooncol. 2009;93(2):279-283.
14. Skottheim I, Stormark K, Christensen H, et al. Significantly altered systemic exposure to atorvastatin
obese patients. Clin Pharmacol Ther. 2009;86(3):311-318.
15. Lipitor. [package insert]. Dublin, Ireland; Pfizer Ireland Pharmaceuticals; 2009.
16. Cellcept. [package insert]. San Francisco, CA; Genentech USA Inc.; 2010.
17. Rapamune. [package insert]. Philadelphia, PA; Wyeth Pharmaceuticals Inc.; 2010.
18. Prograf. [package insert]. Deerfield, IL; Astellas Pharma US, Inc.; 2009.
19. Sobierag D, Wang F, Kirton O. Warfarin resistance after total gastrectomy and Roux-en-Y esophago
2008;28(12):1537-1541.
20. Coumadin. [package insert]. Princeton, NJ; Bristol-Myers Squibb; 2010.
21. Seaman J, Bowers ST, Dixon P, Schindler L. Dissolution of common psychiatric medications in a Ro
2005;46(3):250-253.
Tatyana Lawrecki, Pharm D
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