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Long-Term Changes i...
Long-Term Changes in Cyclosporine Pharmacokinetics After Renal Transplantation in Children : Evidence for Saturable Presystemic Metabolism and Effect of NR1I2 Polymorphism
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- Fanta, Samuel (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Jönsson, Siv (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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- Karlsson, Mats O. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
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Niemi, Mikko (författare)
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Holmberg, Christer (författare)
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Hoppu, Kalle (författare)
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Backman, Janne T. (författare)
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(creator_code:org_t)
- 2013-03-07
- 2010
- Engelska.
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 50:5, s. 581-597
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- To improve cyclosporine dose individualization, the authors carried out a comprehensive analysis of the effects of clinical and genetic factors on cyclosporine pharmacokinetics in 176 children before and up to 16 years after renal transplantation. Pretransplantation test doses of cyclosporine were given intravenously and orally, followed by blood sampling for 24 hours. After transplantation, cyclosporine was quantified at trough, 2 hours postdose, or with dose-interval curves. A 3-compartment population pharmacokinetic model was used to describe the data. Cyclosporine oral bioavailability increased more than 1.5-fold in the first month after transplantation, returning thereafter gradually to its initial value in 1 to 1.5 years. Moreover, older children receiving cyclosporine twice daily as the gelatin capsule microemulsion formulation had an about 1.25 to 1.3 times higher bioavailability than did the younger children receiving the liquid formulation thrice daily. In 91 children with genetic data after transplantation, patients carrying the NR1I2 g.-25385C-g.-24381A-g.205_-200GAGAAG-g.7635G-g.8055C haplotype had about one-tenth lower bioavailability, per allele, than did non-carriers (P = .039). The significance of the NR1I2 genotype warrants further study. In conclusion, by accounting for the effects of developmental factors (body weight), time after transplantation, and cyclosporine dosing frequency/formulation, it may be possible to improve individualization of cyclosporine dosing in children.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- cyclosporine
- pediatric renal transplantation
- population pharmacokinetics
- pharmacogenetics
- therapeutic drug monitoring
- PHARMACY
- FARMACI
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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