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Digoxin Pharmacokin...
Digoxin Pharmacokinetics in Patients with Obesity Before and After a Gastric Bypass or a Strict Diet Compared with Normal Weight Individuals
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- Kvitne, Kine Eide (författare)
- Univ Oslo, Dept Pharm, POB 1068, N-0316 Oslo, Norway.
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- Hovd, Markus (författare)
- Univ Oslo, Dept Pharm, POB 1068, N-0316 Oslo, Norway.
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- Johnson, Line Kristin (författare)
- Vestfold Hosp Trust, Dept Endocrinol Obest & Nutr, Tonsberg, Norway.
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- Wegler, Christine (författare)
- Uppsala universitet,Institutionen för farmaci,AstraZeneca, BioPharmaceut R&D, Res & Early Dev, Cardiovasc Renal & Metab CVRM,DMPK, Gothenburg, Sweden.
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- Karlsson, Cecilia (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,AstraZeneca, Late Stage Dev Cardiovasc Renal & Metab CVRM, BioPharmaceut R&D, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Artursson, Per (författare)
- Uppsala universitet,Institutionen för farmaci
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- Andersson, Shalini (författare)
- AstraZeneca, Oligonucleotide Discovery, Discovery Sci, R&D, Gothenburg, Sweden.
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- Sandbu, Rune (författare)
- Vestfold Hosp Trust, Dept Endocrinol Obest & Nutr, Tonsberg, Norway.
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- Hjelmesaeth, Joran (författare)
- Vestfold Hosp Trust, Dept Endocrinol Obest & Nutr, Tonsberg, Norway.;Univ Oslo, Inst Clin Med, Dept Endocrinol Morbid Obes & Prevent Med, Oslo, Norway.
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- Skovlund, Eva (författare)
- Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, NTNU, Trondheim, Norway.
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- Jansson-Loefmark, Rasmus (författare)
- AstraZeneca, BioPharmaceut R&D, Res & Early Dev, Cardiovasc Renal & Metab CVRM,DMPK, Gothenburg, Sweden.
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- Christensen, Hege (författare)
- Univ Oslo, Dept Pharm, POB 1068, N-0316 Oslo, Norway.
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- Asberg, Anders (författare)
- Univ Oslo, Dept Pharm, POB 1068, N-0316 Oslo, Norway.;Oslo Univ Hosp, Dept Transplantat Med, Oslo, Norway.
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- Robertsen, Ida (författare)
- Univ Oslo, Dept Pharm, POB 1068, N-0316 Oslo, Norway.
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Univ Oslo, Dept Pharm, POB 1068, N-0316 Oslo, Norway Vestfold Hosp Trust, Dept Endocrinol Obest & Nutr, Tonsberg, Norway. (creator_code:org_t)
- Springer, 2024
- 2024
- Engelska.
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Ingår i: Clinical Pharmacokinetics. - : Springer. - 0312-5963 .- 1179-1926. ; 63:1, s. 109-120
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- Background and Objective: Several drugs on the market are substrates for P-glycoprotein (P-gp), an efflux transporter highly expressed in barrier tissues such as the intestine. Body weight, weight loss, and a Roux-en-Y gastric bypass (RYGB) may influence P-gp expression and activity, leading to variability in the drug response. The objective of this study was therefore to investigate digoxin pharmacokinetics as a measure of the P-gp phenotype in patients with obesity before and after weight loss induced by an RYGB or a strict diet and in normal weight individuals.Methods: This study included patients with severe obesity preparing for an RYGB (n = 40) or diet-induced weight loss (n = 40) and mainly normal weight individuals scheduled for a cholecystectomy (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day) followed by an additional 6 weeks of <800 kcal/day induced by an RYGB (performed at week 3) or a very-low-energy diet. Follow-up time was 2 years, with four digoxin pharmacokinetic investigations at weeks 0, 3, and 9, and year 2. Hepatic and jejunal P-gp levels were determined in biopsies obtained from the patients undergoing surgery.Results: The RYGB group and the diet group had a comparable weight loss in the first 9 weeks (13 +/- 2.3% and 11 +/- 3.6%, respectively). During this period, we observed a minor increase (16%) in the digoxin area under the concentration-time curve from zero to infinity in both groups: RYGB: 2.7 mu g h/L [95% confidence interval (CI) 0.67, 4.7], diet: 2.5 mu g h/L [95% CI 0.49, 4.4]. In the RYGB group, we also observed that the time to reach maximum concentration decreased after surgery: from 1.0 +/- 0.33 hours at week 3 to 0.77 +/- 0.08 hours at week 9 (-0.26 hours [95% CI -0.47, -0.05]), corresponding to a 25% reduction. Area under the concentration-time curve from zero to infinity did not change long term (week 0 to year 2) in either the RYGB (1.1 mu g h/L [-0.94, 3.2]) or the diet group (0.94 mu g h/L [-1.2, 3.0]), despite a considerable difference in weight loss from baseline (RYGB: 30 +/- 7%, diet: 3 +/- 6%). At baseline, the area under the concentration-time curve from zero to infinity was -5.5 mu g h/L [95% CI -8.5, -2.5] (-26%) lower in patients with obesity (RYGB plus diet) than in normal weight individuals scheduled for a cholecystectomy. Further, patients undergoing an RYGB had a 0.05 fmol/mu g [95% CI 0.00, 0.10] (29%) higher hepatic P-gp level than the normal weight individuals.Conclusions: Changes in digoxin pharmacokinetics following weight loss induced by a pre-operative low-energy diet and an RYGB or a strict diet (a low-energy diet plus a very-low-energy diet) were minor and unlikely to be clinically relevant. The lower systemic exposure of digoxin in patients with obesity suggests that these patients may have increased biliary excretion of digoxin possibly owing to a higher expression of P-gp in the liver.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Näringslära (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Nutrition and Dietetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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Kvitne, Kine Eid ...
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Hovd, Markus
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Johnson, Line Kr ...
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Wegler, Christin ...
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Karlsson, Cecili ...
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Artursson, Per
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Andersson, Shali ...
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Sandbu, Rune
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Hjelmesaeth, Jor ...
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Skovlund, Eva
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Christensen, Heg ...
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Asberg, Anders
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Robertsen, Ida
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