Χορήγηση φαρμακολογικών δόσεων λεβοθυροξίνης σε ασθενείς με κλινικά σοβαρή παχυσαρκία, πριν και μετά από βαριατρικές επεμβάσεις: ένα μοντέλο μελέτης των θέσεων απορρόφησης από το γαστρεντερικό σύστημα και της φαρμακοκινητική της

Abstract

Levothyroxine (LT4) has a narrow therapeutic window so that slightly changes in the treatment dosecould have significant clinical consequences. Suppressive or replacement doses of LT4 are affected bythe rate and extend of the active ingredient absorbed, as well as by the lean body mass. Concerningthe absorption sites of levothyroxine, the data are limited and our knowledge based on studies of radioisotopic thyroxin in intestinal tract. Aim of this study was to determine the pharmacokinetic parameter ofLT4 in severely obese individuals, compare them with similar data in lean control subjects, as well as tostudy the consequences of bariatric surgery on the pharmacokinetic parameters of LT4 and to identifythe parts of the gastrointestinal tract implicated in its absorption. Method. We studied 62 euthyroidsubjects, who had negative tests for anti-thyroid peroxidase antibodies. Thirty eight of these wereseverely obese but otherwise healthy (SOS-group). Twenty four were healthy controls subjects (controlgroup). Thirty two subjects of the SOS group, underwent sleeve gastrectomy (SG; n=10); Roux-en-Ygastric bypass (RYGBP;n=7) or biliopancreatic diversion with gastric bypass and long limbs (BPDLL;n=15).Subjects received 600mcg oral solution of sodium LT4 after an overnight fast. Serum T4 andT3 were measured 0; 0.5; 1; 1.5; 2; 2.5; 3 and 4 hours after LT4 administration. The same procedurewas repeated 35 days after surgery. Results. The Area Under the Curve (AUC) and the peak plasmaConcentration (Cmax) of T4 after LT4 administration were lower; whereas the Time to reach Cmax(Tmax) from the baseline was higher in the SOS than in the control group. Following surgery; in the SGgroup; the mean AUC was higher (p<0.01); whereas Cmax and Tmax were similar to pre surgery. Inthe RYGBP group; mean AUC; Cmax und Tmax were similar. In the BPD-LL group; mean AUC andCmax were higher 35 days after surgery than before (p<0.001); whereas Tmax was similar.Conclusions. Severely obese individuals may need higher LT4 suppressive or replacement doses thannormal weight individuals due, among other factors, impaired LT4 pharmacokinetic parameters. Thepharmacokinetic parameters of LT4 absorption are improved following bariatric procedures that resultin malabsorption.T4 is absorbed primarily from lower part of the jejunum and from the ileum, whereasstomach and duodenum are not involved directly in the absorption of LT4.