Pharmacokinetic advantages of two-hour post-dose cyclosporin a level for the therapeutic drug monitoring in stable Chinese kidney transplant recipients.
BACKGROUND
Recent studies in Caucasian patients show that 2-hour post-dose cyclosporin A level (C2) monitoring has excellent correlation with the actual drug exposure and risk of rejection. However, the reliability of using C2 in stable Chinese renal transplant patients is unknown.


METHODS
Forty-nine stable Chinese renal transplant patients receiving microemulsion cyclosporin A (Neoral) as part of their immunosuppressive therapy were recruited. Area under the time-concentration curve (AUC) was determined from whole blood cyclosporin A level taken at 0, 1, 2, 4 and 6 h post-dose at time 0 month. Cyclosporin A levels were repeated at 0, 1 and 2 h post-dose at 1 and 2 months later to determine the intra-individual variation at these specific time points.


RESULTS
The average duration of transplantation was 77 +/- 42 months, with average daily cyclosporin dosage of 200 +/- 43 mg in two divided doses. AUC has excellent correlations with cyclosporin A level at 1 h (C1) and 2 h (C2) (r = 0.81 and 0.82 respectively, p < 0.001 for both). The correlation between AUC and trough cyclosporin A level (C0) was statistically significant but only modest (r = 0.52, p < 0.001). On the other hand, the intra-individual coefficient of variation (CVw) of C1 was significantly larger than that of C2 (34.4 +/- 24.2 vs. 15.9 +/- 8.3%, p < 0.0001).


CONCLUSIONS
We conclude that C2 level has favorable pharmacokinetic properties for therapeutic drug monitoring in stable Chinese transplant recipients. Both C1 and C2 have excellent correlation with AUC, but the intra-individual variability of C2 is much lower than that of C1.
Leung
Chi-Bon
CB
Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China. cbleung@alumni.cuhk.net
Szeto
Cheuk-Chun
CC
Ho
Chung-Shun
CS
Law
Wai-Keung
WK
Lam
Christopher Wai-Kei
CW
Li
Philip Kam-Tao
PK
D000368:Aged; D019540:Area Under Curve; D016572:Cyclosporine / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
D007166:Immunosuppressive Agents; D016572:Cyclosporine