Abbreviated kinetic profiles in area-under-the-curve monitoring of cyclosporine therapy. Technical note.
BACKGROUND
The new microemulsion formulation of cyclosporine (CsA-ME) displays more consistent pharmacokinetic properties than the original formulation and may allow successful implementation of an abbreviated area-under-the-curve (AUC) strategy.


METHODS
Here we compared two limited sampling strategies in order to define the one that best predicts AUC after CsA-ME in 51 renal transplant recipients with stable renal function. Pharmacokinetics were based on analysis of blood samples collected over 12 hours after drug administration by high-performance liquid chromatography (HPLC). Predicted AUC was estimated by using a three-point (0, 1 and 3 hr) or a two-point (2 and 6 hr or 0 and 2 hr) sampling strategy.


RESULTS
A simplified strategy with three time points of blood collection at 0, 1, and 3 hours after CsA-ME allowed adequate and accurate prediction of the daily exposure to CsA. AUC prediction with two-point sampling at 2 and 6 hours was less good with a very large error in prediction (only 59% of the estimated AUC were within the accepted range). This limitation was even more evident when the 0 and 2 hour time points were examined, in which only 51% of AUC estimates were included in the accepted range of variation (-10 to 10%).


CONCLUSIONS
A limited strategy of three-point sampling taken early after dosing allows an excellent and perfectly reliable prediction of the actual AUC.
Gaspari
F
F
Department of Transplant Immunology and Innovative Antirejection Therapies, Ospedali Riuniti Bergamo, Mario Negri Institute for Pharmacological Research, Italy. gaspari@irfmn.mnegri.it
Perico
N
N
Signorini
O
O
Caruso
R
R
Remuzzi
G
G
D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D004655:Emulsions; D005260:Female; D005544:Forecasting; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D007700:Kinetics; D008297:Male; D011182:Postoperative Care; D012044:Regression Analysis
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine