Published: 3 September 2020

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Gastrointestinal surgery – Consider possible effects on medicine pharmacokinetics

Published: 3 September 2020
Prescriber Update 41(3): 51
September 2020

Background

Bariatric surgery is becoming more common in New Zealand.¹ Both bariatric surgery and surgical management of intestinal disorders such as inflammatory bowel disease have the potential to significantly affect medicine pharmacokinetics, including absorption.

The potential effects of gastrointestinal surgery on medicine pharmacokinetics can be complex. Most often, absorption is decreased, resulting in decreased efficacy. Reduced medicine absorption can be easily overlooked as an explanation for lack of efficacy. However, there is minimal information on this issue in medicine data sheets and the scientific literature.^2–4

Bariatric surgery

Bariatric surgeries can be classified as restrictive, such as gastric banding and sleeve gastrectomy, malabsorptive or both, such as Roux-en-Y gastric bypass. Restrictive surgeries reduce the volume of food that can be consumed at one time. Malabsorptive procedures create a diversion around portions of the digestive tract.^3–5

Intestinal surgery

Surgical management of intestinal conditions can alter the gastrointestinal surface anatomy, physiology and length.² Any shortening of the intestine resulting from surgery has the potential to decrease medicine absorption. Compared to patients with a small intestinal stoma, colostomy patients are less likely to experience significant absorption problems with normal medicine doses and formulations.² Damage to the intestinal surface or blood flow may also affect medicine absorption.

Effects on pharmacokinetics

Absorption

Although medicines can be absorbed throughout the entire gastrointestinal tract, most absorption occurs in the upper small intestine due to the large surface area, relatively high blood flow and optimal pH for drug absorption. Absorption in the large intestine is generally confined to slow-release formulations of medicines and medicines where the primary effect is in the large intestine.²

Release (disintegration of the tablet or capsule) and dissolution of the active ingredient are the first steps of the absorption process. Although few medicines are absorbed from the stomach, disintegration of the tablet or capsule usually starts in the stomach. A reduction in the stomach surface area with resulting shorter gastric transit time and reduced acid secretion can have important effects on the dissolution of the active ingredients of medicines.⁴ Lower gastric volumes likely reduce absorption due to the decrease in solvent volume available to dissolve the medicine.³ Enteric-coated medicines may require the acidic environment of the stomach to dissolve the coating before the active ingredient can be absorbed in the intestine.^4,5 Reduction in food intake will reduce the absorption of medicines that require food to increase their bioavailability, such as rivaroxaban.⁵

Surgical procedures that rearrange gut anatomy or shorten the small intestine may reduce the absorption of lipophilic medicines that require the presence of bile salts. Altered exposure to bile salts in the small intestine may also affect the enterohepatic cycle, which is important for medicines such as digoxin. ⁴

In summary, absorption of medicines can be affected by:^2–5

• change in gastric motility
• decreased gastric volume
• decreased food content
• decreased acid in the stomach
• decreased surface area/length of the small intestine
• bypass of bile secretions (malabsorptive bariatric surgery)
• disruption of the enterohepatic cycle
• bypass of carrier/uptake/transporter proteins (malabsorptive bariatric surgery)
• integrity of the mucosa.

Additional effects due to weight loss

When significant weight loss is intended or a consequence of surgery, there can be additional pharmacokinetic effects. Many patients experience hypoalbuminemia after bariatric surgery,⁶ which may affect highly protein bound medicines. Clearance of medicines also tends to change with significant weight loss.⁵

In summary, additional pharmacokinetic effects may include:^3,5

• changes in first pass metabolism (possible decrease after malabsorptive surgery and possible increase after weight loss)
• changes in volume of distribution due to loss of fatty tissue following weight loss
• changes to the clearance of medicines due to weight loss
• decrease in plasma albumin concentrations.

Strategies for medicine management

Since changes in medicine pharmacokinetics are difficult to predict, an individualised approach is needed. It should also be noted that that changes to medicine absorption may be temporary or permanent and may develop over time post-surgery.³ See Table 1 for suggested medicine management strategies.

Pharmacists or medicines information services can provide advice on the pharmacokinetics of medicines and alternative formulations for individual patients.²

Table 1: Suggested strategies for management of medicines following gastrointestinal surgerya–c
Switch critical medicines to non-oral forms, eg, an oral contraceptive can be changed to an implant or IUD.
Switch critical medicines to those which can be closely monitored for efficacy or safety, eg, if anticoagulation is needed warfarin may be preferable to dabigatran or rivaroxaban.
Switch to a liquid dose form or dissolvable or crushable tablets if no non-oral form is available. Check the osmolarity, excipients and medicine volume required of the oral form as some hyperosmolar products (particularly those containing sorbitol as a sweetener) can cause osmotic diarrhoea.
Dose by weight, particularly if significant weight loss is anticipated.
Avoid using extended release formulations or enteric coated medicines.
Use medicines with low first-pass metabolism if possible.
Consider increasing the dose if efficacy is reduced.

Sources:

1. Sood S, Tanner F, Testro A. 2013. Prescribing for a patient with reduced intestinal length. Australian Prescriber 36: 136–8. URL: nps.org.au/australian-prescriber/articles/prescribing-for-a-patient-with-reduced-intestinal-length (accessed 1 July 2020).
2. Lorico S, Colton B. 2020. Medication management and pharmacokinetic changes after bariatric surgery. Canadian Family Physician 66(6): 409–16. URL: cfp.ca/content/66/6/409 (accessed 1 July 2020).
3. Santamaría MM, Villafranca JJA, Abilés J, et al. 2018. Systematic review of drug bioavailability following gastrointestinal surgery. European Journal of Clinical Pharmacology 74(12): 1531–45. DOI: 10.1007/s00228-018-2539-9 (accessed 2 July 2020).

References

1. Garrett M, Poppe K, Wooding A, et al. 2020. Private and public bariatric surgery trends in New Zealand 2004–2017: demographics, cardiovascular comorbidity and procedure selection. Obesity Surgery 30(6): 2285–93. DOI: 10.1007/s11695-020-04463-x (accessed 2 July 2020).
2. Sood S, Tanner F, Testro A. 2013. Prescribing for a patient with reduced intestinal length. Australian Prescriber 36: 136–8. URL: nps.org.au/australian-prescriber/articles/prescribing-for-a-patient-with-reduced-intestinal-length (accessed 1 July 2020).
3. Lorico S, Colton B. 2020. Medication management and pharmacokinetic changes after bariatric surgery. Canadian Family Physician 66(6): 409–16. URL: www.cfp.ca/content/66/6/409 (accessed 1 July 2020).
4. Santamaría MM, Villafranca JJA, Abilés J, et al. 2018. Systematic review of drug bioavailability following gastrointestinal surgery. European Journal of Clinical Pharmacology 74(12): 1531–45. DOI: 10.1007/s00228-018-2539-9 (accessed 2 July 2020).
5. Martin KA, Lee CR, Farrell TM, et al. 2017. Oral anticoagulant use after bariatric surgery: a literature review and clinical guidance. American Journal of Medicine 130(5): 517–24. DOI: 10.1016/j.amjmed.2016.12.033 (accessed 25 June 2020).
6. Stein J, Stier C, Raab H, et al. 2014. Review article: the nutritional and pharmacological consequences of obesity surgery. Alimentary Pharmacology and Therapeutics 40(6): 582–609. DOI: https://doi.org/10.1111/apt.12872 (accessed 2 July 2020).