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- Hovd, M., et al.
(författare)
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Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance
- 2023
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 62:5, s. 725-735
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionRosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity.MethodsPatients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic investigations. Both groups underwent a 3-week low-energy diet (LED; < 1200 kcal/day), followed by RYGB or a 6-week very-low-energy diet (VLED; < 800 kcal/day).ResultsA total of 80 patients were included in the RYGB group (40 patients) and diet-group (40 patients). The weight loss was similar between the groups following LED and RYGB. The LED induced a similar (mean [95% CI]) decrease in CL/F in both intervention groups (RYGB: 16% [0, 31], diet: 23% [8, 38]), but neither induced VLED resulted in any further changes in CL/F. At Year 2, CL/F had increased by 21% from baseline in the RYGB group, while it was unaltered in the diet group. Patients expressing the reduced function SLCO1B1 variants (c.521TC/CC) showed similar changes in CL/F over time compared with patients expressing the wild-type variant.ConclusionsNeither body weight, weight loss nor RYGB per se seem to affect OATP1B1 activity to a clinically relevant degree. Overall, the observed changes in rosuvastatin pharmacokinetics were minor, and unlikely to be of clinical relevance.
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| 2. |
- Stenberg, Patric, et al.
(författare)
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Theoretical predictions of drug absorption in drug discovery and development
- 2002
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Ingår i: Clinical Pharmacokinetics. - : Adis International. - 0312-5963 .- 1179-1926. ; 41:11, s. 877-899
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Tidskriftsartikel (refereegranskat)abstract
- The clinical development of new drugs is often terminated because of unfavourable pharmacokinetic properties such as poor intestinal absorption after oral administration. Intestinal permeability and solubility are two of the most important factors that determine the absorption properties of a compound. Efficient and reliable computational models that predict these properties as early as possible in drug discovery and development are therefore desirable. In this review, we first discuss the implementation of predictive models of intestinal drug permeability and solubility in drug discovery and development. Secondly, we discuss the mechanisms of intestinal drug permeability and computational methods that can be used to predict it. We then discuss factors influencing drug solubility and models for predicting it. We finally speculate that once these and other predictive computational models are implemented in drug discovery and development, these processes will become much more effective. Further, an increased fraction of drug candidates that are less likely to fail during clinical development will be selected.
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