Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy

Diwan, Tayyab S.; Lichvar, Alicia; Leino, Abbie D.; Vinks, Alexander A.; Christians, Uwe; Cardi, M.; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Kaiser, Tiffany E.; Woodle, E. Steve; Alloway, Rita R.

doi:10.1111/ctr.12975

Cited by 23 publications

(24 citation statements)

References 28 publications

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“…17 All previous publications regarding the PK of immunosuppression have been conducted only after bariatric surgery. 7,8 This study demonstrates that in the post-LSG period, there is a significant increase in the drug exposure, as reflected by the AUC 24 and AUC ∞ , for the 4 medications. An augmented drug exposure will need to be considered in the dose management of immunosuppression for any recipient or candidate undergoing LSG.…”

Section: Discussionmentioning

confidence: 66%

“…LSG restricts the functional gastric volume to a narrow tube along the lesser curve without malabsorption. 8 Tacrolimus and MMF have very different PK characteristics, so LSG and weight loss might affect them differently. 5,6 A major concern for potential transplant patients is the possible changes to absorption and effectiveness of oral immunosuppressive agents.…”

Section: Introductionmentioning

confidence: 99%

“…Neither formulation affected the bioavailability of MMF. 8 Tacrolimus and MMF have very different PK characteristics, so LSG and weight loss might affect them differently. In healthy volunteers, tacrolimus oral bioavailability averages 20%, 9 but it ranges from 4% to 89% due to an extensive gut first-pass effect, primarily dependent upon CYP3A4/5, MDR1, or P-glycoprotein, and poor solubility.…”

Section: Introductionmentioning

confidence: 99%

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Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy

Chan

Hajjar

Boutin

et al. 2020

American Journal of Transplantation

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Abbreviations: AUC 24 , area under the plasma concentration vs time curve from 0 to 24 hours; AUC ∞ , area under the plasma concentration vs time curve from 0 to infinity; BMI, body mass index; Cl/F, apparent total plasma clearance; C max , maximum observed plasma concentration; EBW, excess body weight; EBWL, excess body weight loss; EC-MPS, enteric-coated mycophenolate sodium; ER-tac, extended-release tacrolimus; ESRD, end-stage renal disease; F, the relative drug exposure or fraction of the dose available in the body during an interval of time, as reflected by AUC 24 or AUC ∞ ; LSG, laparoscopic sleeve gastrectomy; MMF, mycophenolate mofetil; MPA, mycophenolic acid; MPAG, MPA glucuronides; PK, pharmacokinetics; t ½ , terminal elimination half-life; T max , time to maximum concentration; UGT, UDP-gluco-uronosyltransferase; V z /F, apparent volume of distribution. Funding information Astellas PharmaLaparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time.A prospective, single-dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended-release tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m 2 with an excess body weight loss of 54.9%. The AUC 24 of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended-release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects. K E Y W O R D Sclinical research/practice, complication: medical/metabolic, kidney transplantation/ nephrology, obesity, pharmacokinetics/pharmacodynamics, pharmacology, recipient selection

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy

Chan

Hajjar

Boutin

et al. 2020

American Journal of Transplantation

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“…However, because LSG results in similar weight loss and metabolic improvement but with less risk of complications, it is increasingly the preferred choice, particularly in a complex patient population such as LT recipients . Concerns with altered drug absorption and the need for increased dosages of IS medications, in addition to the hypovitaminoses associated with RYGB, also support the use of LSG . A final benefit of LSG compared with RYGB is preserved access to the biliary tree for a potential future need for endoscopic evaluation of the allograft liver.…”

Section: Discussionmentioning

confidence: 99%

“…As previously demonstrated via pharmacokinetic and pharmacogenetic analyses, dose modifications of IS agents after LSG are likely unnecessary . However, during the early post‐LSG period when the patient is only consuming liquids and may experience symptoms (ie, nausea, vomiting, and diarrhea) that could impact drug absorption, temporary adjustments to their IS regimens are employed.…”

Section: Methodsmentioning

confidence: 99%

Delayed Sleeve Gastrectomy Following Liver Transplantation: A 5‐Year Experience

et al. 2019

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Obesity has become an epidemic in the United States over the past decade, and recent studies have shown this trend in the liver transplantation (LT) population. These patients may be candidates for laparoscopic sleeve gastrectomy (LSG) to promote significant and sustained weight loss to prevent recurrence of nonalcoholic steatohepatitis. However, safety remains a concern, and efficacy in this setting is uncertain. A single‐institution database from 2014 to 2018 was queried for patients undergoing LSG following LT. The selection criteria for surgery were consistent with National Institutes of Health guidelines, and patients were at least 6 months after LT. A total of 15 patients (median age, 59.0 years; Caucasian, 86.7%; and female, 60%) underwent LSG following LT. Median time from LT to LSG was 2.2 years with a median follow‐up period of 2.6 years. The median hospital length of stay (LOS) was 2 days after LSG. Mortality and rate of liver allograft rejection was 0, and there was 1 postoperative complication (a surgical site infection). Following LSG, body mass index (BMI) decreased from 42.7 to 35.9 kg/m2 (P < 0.01), and in 12 patients with at least 1 year of follow‐up, the total body weight loss was 20.6%. Following LSG in patients with diabetes, the median daily insulin requirements decreased from 98 (49‐118) to 0 (0‐29) units/day (P = 0.02), and 60% discontinued insulin. Post‐LT patients had a similar decrease in BMI and reduction in comorbidities at 1 year compared with a matched non‐LT patient cohort. In the largest patient series to date, we show that LSG following LT is safe, effective, and does not increase the incidence of liver allograft rejection. Larger longer‐term studies are needed to confirm underlying metabolic changes following LSG.

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Bariatric Surgery in the Peritransplant Period

Pomenti

Mehta

Guo

et al. 2021

Clinical Liver Disease

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Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy

Abstract: Dose modification of immunosuppressants post-LSG may not be necessary aside from standard therapeutic drug monitoring.

Cited by 23 publications

References 28 publications

Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy

Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy

Delayed Sleeve Gastrectomy Following Liver Transplantation: A 5‐Year Experience

Bariatric Surgery in the Peritransplant Period

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