Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy.
Laparoscopic 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/m2 with an excess body weight loss of 54.9%. The AUC24 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.
['Chan|Gabriel|G|0000-0002-0997-1028', 'Hajjar|Roy|R|', 'Boutin|Lucie|L|', 'Garneau|Pierre Y|PY|', 'Pichette|Vincent|V|', 'Lafrance|Jean-Philippe|JP|0000-0001-7876-0446', 'Elftouh|Naoual|N|', 'Michaud|Josée|J|', 'du Souich|Patrick|P|']
D005260:Female D005743:Gastrectomy D006801:Humans D007166:Immunosuppressive Agents D007676:Kidney Failure, Chronic D010535:Laparoscopy D008297:Male D008875:Middle Aged D009173:Mycophenolic Acid D009767:Obesity, Morbid D011446:Prospective Studies D016559:Tacrolimus
obesity clinical research/practice complication: medical/metabolic kidney transplantation/nephrology pharmacokinetics/pharmacodynamics pharmacology recipient selection