Impact of Bariatric Surgery on the Pharmacokinetics Parameters of Amoxicillin The effect of bariatric surgery on the direct oral anticoagulant rivaroxaban: the extension study. Spine surgery research: on and beyond current strategies. Pharmacokinetics of Amoxicillin: Dose Dependence After Intravenous, Oral, and Intramuscular Administration
Background Bariatric surgery leads to several anatomo-physiological modifications that may affect pharmacokinetic parameters and consequently alter the therapeutic effect of drugs , such as antibiotics . The pharmacokinetics of oral amoxicillin after Roux-en-Y gastric bypass ( RYGB ) surgery is unknown . Objectives The objective of this study was to evaluate the impact of bariatric surgery on the pharmacokinetics of  amoxicillin . Methods This study was performed as a r and omized , open-label , single-dose clinical trial , with two periods of treatment , in which obese subjects ( n = 8) received an amoxicillin 500 mg capsule orally before and 2 months after the RYGB surgery . The  amoxicillin plasma concentration was determined by liquid chromatography coupled to mass spectrometry ( LC-MS/MS ) . Results After the surgery , the mean weight loss was 17.03 ± 5.51 kg , and mean body mass index ( BMI ) decreased from 46.21 ± 2.82 to 38.82 ± 3.32 kg/m2 . The mean amoxicillin area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration ( AUC0–tlast ) increased significantly ( 3.5-fold ) ; the maximum plasma concentration ( Cmax ) increased 2.8-fold after the bariatric surgery . No correlation was found between amoxicillin absorption , BMI , and weight loss percentage . Conclusion The alterations observed in the amoxicillin pharmacokinetics suggest that obese subjects included in this trial had a substantially increase in amoxicillin systemic exposure after RYGB surgery . However , despite this increase , its exposure was lower than the values reported for non-obese volunteers . Trial Registration Identifiers : BACKGROUND Thromboembolic disease is a potentially serious complication in bariatric surgery patients . Direct oral anticoagulants ( DOAC ) have been investigated in orthopedic surgery patients .  DOAC data after bariatric surgery are still limited to the early postsurgical period . Whether postsurgical midterm adaptations due to anatomic and physiologic alterations influence drug pharmacology is currently not known . OBJECTIVE The aim of this study was to investigate the influence of weight loss and type of bariatric surgery on midterm postsurgical pharmacokinetic and pharmacodynamic parameters of rivaroxaban . SETTING University hospital . METHODS In this monocentric study , bariatric patients received a single oral dose of rivaroxaban ( 10 mg ) 6 to 8 months after sleeve gastrectomy ( SG ) or Roux-en-Y-gastric bypass ( RYGB ) . Pharmacokinetic and pharmacodynamic parameters were assessed and compared with prebariatric surgery results . RESULTS We included 6 RYGB and 6 SG patients .  Percent excess weight loss was 71.4 % ( interquartile range 56.4 , 87.9 ) in the SG group and 76.6 % ( 64.5 , 85.7 ) in the RYGB group . Rivaroxaban mean areas under the curve 6 to 8 months after the bariatric procedure ( 922.4 µg × h/L , coefficient of variation 43.2 ) were comparable to those measured preoperatively ( 952.6 µg × h/L , 16.8 ) . There was no relevant difference between the 2 surgical procedure groups . Rivaroxaban led to a decrease of prothrombin fragments F1 + 2 over 12 hours after oral intake confirming in vivo efficacy . CONCLUSIONS Significant weight loss and altered anatomy after RYGB and SG procedures do not appear to affect the pharmacokinetics and pharmacodynamics of prophylactic rivaroxaban . A single dose of Rivaroxaban was well tolerated and considered safe in this trial BACKGROUND CONTEXT Systematic review s of the literature are powerful tools in evidence -based medicine . However , the design and report of systematic review s in spinal surgery contain many aspects amenable to improvement . PURPOSE To discuss the issues especially relevant for systematic review s in spinal surgery . METHODS From our experience of systematic review s and meta-analyses of clinical trials in  spinal surgery  , we infer guidance for the design and execution of systematic literature review s. RESULTS There are many difficulties associated with the design as well as conduct of clinical trials and consequently appraising evidence in spinal surgery . New treatments should be compared with the gold st and ard before other comparisons are investigated . Studies should present data as thoroughly as possible regarding all subgroups and follow-up moments , possibly in supplementary material . To provide the highest level of evidence , systematic review s should be as rigorously design ed as possible . CONCLUSIONS Gathering information on clinical effectiveness in spinal surgery can be improved both at the clinical study level and at the systematic review level . Alternatives to r and omized controlled trials such as comparative studies can be valuable tools on the clinical effectiveness of treatments in spinal surgery . The experience reflected in this article can support the scientific efforts in this field Amoxicillin was studied in normal subjects after intravenous , oral , and intramuscular administration of 250- , 500- , and 1,000-mg doses .  Serum drug levels were analyzed using a two-compartment open model , as well as area under the curve ( AUC ) and urinary recovery . The variations of these pharmacokinetic parameters were then examined using the three-way analysis of variance and linear regression equations . These results confirmed nearly complete oral absorption : AUC was 93 % of intravenous absorption , and urinary recovery was 86 % . The intramuscular administration of amoxicillin results in complete and reliable absorption with peak drug levels , AUCs , and urinary recovery equivalent to oral dosage . The absorption of lyophilized amoxicillin after intramuscular injection result ed in an AUC that was 92 % of intravenous absorption and urinary recovery of 91 % . The peak serum levels , time to peak , and other pharmacokinetic parameters for intramuscular injection were nearly identical to those for oral administration . Kinetics of both intramuscular and oral administration exhibited dose-dependent absorption ( absorption rate constant , 1.3/h for 250 mg and 0.7/h for 1,000 mg ) . This result ed in relatively later and lower peak serum levels for increasing dose . Total absorption , however , showed no dose dependence , as indicated by urinary recovery and AUC , which changed by less than 10 %
Patients given oral beta-lactams and macrolides warrant close monitoring due to unpredictable absorption post-bariatric surgery , whereas oral fluoroquinolones and linezolid may not be affected .
Several studies also showed decreased absorption following RYGB , as well as lower serum exposure in patients with obesity compared to non-obese controls .
The purpose of this study was to conduct a systematic review of the existing literature to determine the effect of bariatric surgery on various pharmacokinetic parameters of oral antibiotic absorption as well as overall patient outcomes .