Pharmacodynamic monitoring of the conversion of cyclosporine to tacrolimus in heart and lung transplant recipients.
OBJECTIVE
Conversion from cyclosporine (CsA) to tacrolimus (TRL) remains challenging in the daily routine due to individual variations in blood concentrations (pharmacokinetics, PK), pharmacodynamics (PD) and in interactions on plasma mycophenolic acid (MPA) concentrations. Therefore, we used our PD assays of lymphocyte function to monitor the conversion of CsA to TRL in heart (HTx) and lung (LTx) transplant recipients.


METHODS
Patients (six HTx, two LTx) were converted from CsA to TRL because of gingival hyperplasia. All patients were treated with 6 mg BID TRL 24 hours after the last CsA dose and received mycophenolate mofetil BID cotherapy. PK measurements of CsA, TRL, and MPA were done by EMIT. Expression of cytokine production (IL-2, TNF-alpha), lymphocyte proliferation (PCNA), and activation (CD25) was assessed by FACS.


RESULTS
TRL concentrations increased from day 1 to 3, but did not alter MPA concentrations, which were comparably high to MPA concentrations in combination with CsA (day 0). Compared to CsA therapy, increased TRL concentrations did not further inhibit PCNA expression, inhibited CD25 expression less on days 1 and 2 and equally high on day 3, but inhibited expression of IL-2 and TNF-alpha significantly higher on days 2 and 3 (P < .05).


CONCLUSIONS
This study shows that monitoring PD of lymphocyte functions after conversion from CsA to TRL in HTx and LTx recipients revealed differences of inhibition of lymphocyte functions. Monitoring PD of lymphocyte function may provide insights in drug interactions of immunosuppressive combination therapy and may help to tailor immunosuppression to avoid toxicity and to enhance efficacy.
Barten
M J
MJ
University Leipzig, Department of Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany. bartenm@medizin.uni-leipzig.de
Rahmel
A
A
Garbade
J
J
Bold
A
A
Bittner
H B
HB
Dhein
S
S
Mohr
F W
FW
Gummert
J F
JF
D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005882:Gingival Diseases / Q000139:chemically induced / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D006965:Hyperplasia; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016040:Lung Transplantation / Q000276:immunology*; D008657:Metabolic Clearance Rate; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus