Effect of plasma uric acid on pharmacokinetics of cyclosporine A in living-related renal transplant recipients and pharmacokinetic study in rats with experimental hyperuricaemia.
Objectives: Renal transplant recipients are thought to have an increased risk of hyperuricaemia (HU); therefore, the effects of plasma uric acid (UA) on the pharmacokinetics (PK) of cyclosporine A (CyA), an immunosuppressant, in renal transplant recipients and experimental animals were investigated....
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 35; no. 3; pp. 323 - 333 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Jun2010
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105196130&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105196130 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Jun2010 vid: 35 iid: 3 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 105196130 2010649940 10.1111/j.1365-2710.2009.01105.x NLM20831533 105196130 ppf: 323 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Effect of plasma uric acid on pharmacokinetics of cyclosporine A in living-related renal transplant recipients and pharmacokinetic study in rats with experimental hyperuricaemia. aug: au: Sugioka N Takai M Yoshida K Yasuda K Fukushima K Kokuhu T Okamoto M Yoshimura N Takada K affil: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan sug: subj: Cyclosporine Pharmacokinetics Kidney Transplantation Uric Acid Blood Adolescence Adult Aged Animal Studies Biological Availability Cyclosporine Administration and Dosage Descriptive Statistics Female Human Japan Male Middle Age Rats Retrospective Design Unpaired T-Tests Adolescent: 13-18 years Adult: 19-44 years Aged: 65+ years Middle Aged: 45-64 years Female Male ab: Objectives: Renal transplant recipients are thought to have an increased risk of hyperuricaemia (HU); therefore, the effects of plasma uric acid (UA) on the pharmacokinetics (PK) of cyclosporine A (CyA), an immunosuppressant, in renal transplant recipients and experimental animals were investigated. Methods: An open-label, non-randomized, retrospective study was performed in renal transplant recipients. Data from 76 subjects who received a renal transplantation with CyA medication were included. We compared the PK of CyA of recipients showing a high UA level with the other recipients. In addition, PK studies were performed using hyperuricaemic-model rats (HU rats) prepared by subcutaneous injection of the uricase inhibitor, potassium oxonate and intraperitoneal injection of UA. Results: The area under the blood concentration vs. time curve (AUC) up to 9 h, the blood level at 2 h after dose and peak level in high UA recipients (UA > 7·0 mg/dL) was significantly lower (about 10-16%) than that in the other recipients, although there were no differences in dose, and the trough blood level. On the contrary, there were no differences in PK parameters after intravenous administration of CyA between HU and control rats; however, AUC, peak level and bioavailability in HU rats (2·01 ± 0·56 µg h/mL, 0·47 ± 0·26 µg/mL and 0·186 ± 0·05, respectively) after oral administration were significantly lower than in the control animals (6·13 ± 0·97 µg h/mL, 0·82 ± 0·17 µg/mL and 0·458 ± 0·07 µg/mL, respectively). In addition, the absorptions of CyA and midazolam, an ideal probe for CYP3A, from the intestinal loop in HU rats were significantly less (about 50% and 37%, respectively) than in the controls. Conclusions: The absorption of CyA was affected by plasma UA in transplant recipients and experimental rats. The contribution of intestinal metabolism by CYP3A to decreasing CyA absorption in HU rats was significant. These results suggest that transplant recipients with high UA may have poor absorption of CyA. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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