Influence of intra-individual variability of cyclosporine pharmacokinetics on the kidney transplant function at early stage after operation
- VernacularTitle:环孢素A药代动力学的个体差异对术后早期移植肾功能的影响
- Author:
Sen XIE
;
Yunhui CHEN
;
Ligong TANG
- Publication Type:Journal Article
- Keywords:
Kidney transplantation;
Pharmacokinetics;
Cyclosporine;
Graft rejection;
Drug toxicity
- From:
Chinese Journal of Organ Transplantation
2003;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the relationship between individual pharmacokinetics characteristics of cyclosporine (CsA) and the occurrence of acute rejection episodes or CsA-induced nephrotoxicities in kidney transplants. Methods The whole blood CsA concentrations were assayed 7 days after oral admi- nistration with a dosage of 6 mg/kg daily in 47 recipients. The blood samples drawn just prior to ingestion of the dose and subsequently at 1, 2, 3, 4, 5, 6, 8, 10, 12 h later were monitored with TDX. Recipients were grouped according to the varied situations of kidney transplant functions within one month after pharmacokinetics monitoring. Pharmacokinetics parameters of C_0, C_ max , T_ max , CL/F, T_ 1/2(a) , T_ 1/2(e) and AUC in each group were calculated and compared among the groups. Results Of 47 recipients, 12 cases had experienced AR episodes, 7 cases had suffered CsA-NT, and the remaining 26 cases survived with stable graft functions. Major pharmacokinetics parameters in AR group were T_ 1/2(a) , T_ 1/2(e) , CL/F, T_ max and AUC, which were significantly different from the corresponding parameters in the group with stable graft function. Pharmacokinetics curve of AR group was characterized with a earlier T_ max (usually less than 2 h), a sharp absorb peak and a abbreviated AUC, T_ 1/2(e) , CL/F, T_ max , and AUC in CsA-NT group, which was also significantly varied from that in the stable group. The curve of CsA-NT group, with a delayed T_ max (often more than 2 h), a broad absorb peak or double peaks, however, was predominantly distinguished from the previous AR curve. Levels of C_0 in the three groups were comparable when AR or CsA-NT occurred. Conclusion Pharmacokinetics monitoring accomplished by multiple point CsA level samples over the entire 12 h dosing interval is a more accurate assessment for drug exposure. It is suggested that patients who absorb and eliminate CsA quickly are likely to experience AR episodes. Meanwhile, those poor eliminators are at risk to suffer CsA-NT.
