Objective: Sirollmus (RAPA) is a new immunosuppressive drug currently
in Phase III clinical trials in combination with cyclosporine A (CsA).
The toxicity profiles for CsA and PAPA are only partially overlapping
, with RAPA toxicity consisting primarily of hyperlipidemia and myelod
epression but without the nephrotoxicity, neurotoxicity, and hepatotox
icity, which are seen with CsA. Patients in the clinical trial are bei
ng monitored using HPLC or LC/MS/MS assays; there is no immunoassay fo
r PAPA reported to date. We have previously reported a radioreceptor a
ssay (RRA) for PAPA, which has an excellent correlation with the HPLC
assay (r = 0.997). The RRA has several advantages including excellent
precision, sensitivity, rapid turnaround time, and a one-step extracti
on procedure. We report the evaluation of blood samples from patients
who were exhibiting RAPA toxicity and comparison of the RRA results wi
th the HPLC results. Methods: EDTA whole blood specimens (n = 42) were
obtained from six renal transplant recipients taking RAPA and CsA and
exhibiting decreased platelet counts. Thirty-two samples from patient
s without decreased platelet counts were also received. The samples we
re analyzed with the RRA and the results were compared to those obtain
ed with the HPLC assay. Results: By HPLC, the results ranged from 3.2-
72.6 mu g/L RAPA with 43% of the results greater than or equal to 30 m
u g/L. With the RRA, the range was 7.7-83.0 mu g/L RAPA equivalents, w
ith 60% of the results greater than or equal to 30 mu g/L. The RRA res
ults are distinctly higher than the HPLC results all along the range.
The correlation between the two assays was 0.861, with a slope of 0.96
6 and a Y-intercept of 11.1. Conclusion: Since the RRA is consistently
higher than HPLC concentration in patients with decreased platelet co
unts, but correlates well in patients with no signs of toxicity, the R
RA may be useful for monitoring patients for toxicity, by giving a bet
ter indication of increasing degree of immunosuppression than the HPLC
assay.