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

Abstract

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

Obesity in work-up of kidney transplant candidates – review of clinical practice guidelines.

“…Complication rates of LSG were similar between patients with and without ESKD [23,44]. It should be noticed that LSG performed before transplantation is associated with significant changes of pharmacokinetics of tacrolimus and mycophenolate mofetil (increased maximal concentration and decreased clearance) in that group of patients [45]. Whereas malabsorptive procedures are related to hyperoxaluria and increased risk of nephrolithiasis [46].…”

Clinical and Economic Impact of Previous Bariatric Surgery on Liver Transplantation: a Nationwide, Population-Based Retrospective Study

“…RYGB was the most frequent BS procedure, performed in 53.9% of cases, followed by SG (35.9%), which is surprising as in France SG overcame the RYGB in 2010 as the most performed procedure [ 2 ]. Furthermore, we highlight that SG may be advantageous over RYGB in this setting for the absorption of immunosuppressive drugs [ 29 ], even if close monitoring after SG to avoid possible overdosing is recommended by some authors [ 30 ].…”

Management of obesity in kidney transplant candidates and recipients: A clinical practice guideline by the DESCARTES Working Group of ERA

“…Also, sleeve gastrectomy does not affect oxalate absorption since it does not modify intestinal absorption [ 103 ]. However, there are suggestions of altered pharmacokinetics through decreased drug clearance due to increased drug exposure or decreased liver metabolism [ 116 ].…”