Prediction of flucytosine-induced thrombocytopenia using creatinine clearance.
OBJECTIVE
To evaluate and investigate the efficacy and accuracy of an earlier derived relationship between thrombocyte nadir and mean creatinine clearance in order to make it possible to predict flucytosine (5-FC)-related thrombocytopenia.


METHODS
The earlier derived relationship between thrombocyte nadir and mean creatinine clearance is validated using a patient population of 35 intensive care unit (ICU) patients. Patients have to meet the inclusion criteria as defined in the initial study (i.e., developing thrombocytopenia during 5-FC treatment or remaining within the normal thrombocyte range; individual pharmacokinetic parameters within certain limits; a minimum of three measured 5-FC serum levels).


RESULTS
Of a total of 35 patients, 11 are eligible since they meet the inclusion criteria as defined in the initial study. A significant relationship between the observed and predicted thrombocyte nadir values can be derived: Y(pred) = 0.608.X(obs) + 24. 330 (r = 0.615; t(obs) = 2.337; t at p < 0.05 and 9 degrees of freedom = 2.262). The predicted value of the thrombocyte nadir corresponds with a mean prediction error (bias) of -18.3 (95% CI -45.9; 9.4) and a root mean squared prediction error (precision) of 48.3 (95% CI 23.9-63.9).


CONCLUSIONS
The earlier derived relationship between thrombocyte nadir and mean creatinine clearance is accurate and precise. However, due to the strict inclusion criteria used to derive and validate this relationship, it cannot be applied to all 5-FC-treated patients.
Vermes
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Department of Clinical Pharmacy, Academic Medical Center, University of Amsterdam, The Netherlands.
Guchelaar
H J
HJ
Dankert
J
J
D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects*; D003404:Creatinine / Q000652:urine*; D005260:Female; D005437:Flucytosine / Q000009:adverse effects*; D005544:Forecasting; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013921:Thrombocytopenia / Q000139:chemically induced*
D000935:Antifungal Agents; D003404:Creatinine; D005437:Flucytosine