Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients

Sweta Tandra, Naga Chalasani, David R. Jones, Samer Mattar, Stephen D. Hall, Raj Vuppalanchi

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)262-269
Number of pages8
JournalAnnals of Surgery
Volume258
Issue number2
DOIs
StatePublished - Aug 2013
Externally publishedYes

Fingerprint

Gastric Bypass
Pharmacokinetics
Urine
Tolbutamide
Omeprazole
Sodium
Midazolam
Furosemide
Caffeine
Pharmaceutical Preparations
Dextromethorphan
Natriuresis
Biological Availability
Area Under Curve
Half-Life
Enzymes

Keywords

  • CYP3A
  • drug metabolism
  • furosemide
  • gastric bypass
  • oral cocktail

ASJC Scopus subject areas

  • Surgery

Cite this

Tandra, S., Chalasani, N., Jones, D. R., Mattar, S., Hall, S. D., & Vuppalanchi, R. (2013). Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. Annals of Surgery, 258(2), 262-269. https://doi.org/10.1097/SLA.0b013e31827a0e82

Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. / Tandra, Sweta; Chalasani, Naga; Jones, David R.; Mattar, Samer; Hall, Stephen D.; Vuppalanchi, Raj.

In: Annals of Surgery, Vol. 258, No. 2, 08.2013, p. 262-269.

Research output: Contribution to journalArticle

Tandra, S, Chalasani, N, Jones, DR, Mattar, S, Hall, SD & Vuppalanchi, R 2013, 'Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients', Annals of Surgery, vol. 258, no. 2, pp. 262-269. https://doi.org/10.1097/SLA.0b013e31827a0e82
Tandra, Sweta ; Chalasani, Naga ; Jones, David R. ; Mattar, Samer ; Hall, Stephen D. ; Vuppalanchi, Raj. / Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients. In: Annals of Surgery. 2013 ; Vol. 258, No. 2. pp. 262-269.
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AU - Vuppalanchi, Raj

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N2 - 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.

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