title: Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
abstract: OBJECTIVE
  We conducted a pharmacokinetic (PK) study and a pharmacodynamic (PD) study to assess whether Roux-en-Y gastric bypass (RYGB) surgery is associated with significant changes to PK and PD of oral medications.
  
  
  BACKGROUND
  The effect of RYGB on oral drug disposition is not well understood.
  
  
  METHODS
  An oral cocktail of probe drugs for major drug-metabolizing enzymes (caffeine, tolbutamide, omeprazole, dextromethorphan, and oral and intravenous midazolam) was administered to 18 RYGB recipients and 18 controls. Timed blood and urine samples were obtained for PK analyses. Forty mg of oral furosemide was administered to 13 RYGB recipients and 14 controls, and urine and blood samples were collected for assessing furosemidePK, and urine volume and urine sodium excretion for PD analyses.
  
  
  RESULTS
  Compared with controls, the RYGB group had significantly lower time to maximum plasma concentration (tmax) for caffeine (0.58 ± 0.5 vs 2.1 ± 2.2 hours, P < 0.0001), tolbutamide (1.4 ± 1.8 vs 2.1 ± 2.2 hours, P = 0.0001), omeprazole (1.1 ± 1.1 vs 4.4 ± 1.3 hours, P < 0.0001), and oral midazolam (0.5 ± 0.2 vs 0.7 ± 0.4 hours, P < 0.01). However, maximum plasma concentration, half-life, area under the curve, and oral bioavailability were not different. Compared with controls, the RYGB group had brisk natriuresis, with significantly lower tmax for urine sodium (1.3 ± 0.5 vs 3.1 ± 2.3 hours, P < 0.02) and correspondingly lower tmax for furosemide (1.8 ± 0.3 vs 4.2 ± 1.2 hours, P = 0.006). However, 6-hour urine sodium and 6-hour urine volume were not different between the two groups.
  
  
  CONCLUSIONS
  RYGB recipients have significantly shorter tmax for the studied orally administered medications, but otherwise no other significant changes in PK were reported.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sweta
authors.initials: S
authors.lastname: Tandra
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Samer
authors.initials: S
authors.lastname: Mattar
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hall
authors.forename: Raj
authors.initials: R
authors.lastname: Vuppalanchi
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D001711:Biotransformation; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003915:Dextromethorphan / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D018757:GABA Modulators / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D015390:Gastric Bypass; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D010599:Pharmacokinetics; D053719:Tandem Mass Spectrometry; D014044:Tolbutamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D000697:Central Nervous System Stimulants; D004232:Diuretics; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D007004:Hypoglycemic Agents; D002110:Caffeine; D003915:Dextromethorphan; D005665:Furosemide; D014044:Tolbutamide; D009853:Omeprazole; D008874:Midazolam