RESUMO
Itraconazole possesses nonlinear pharmacokinetics. We used the Michaelis-Menten model for calculating dosing rates under steady-state conditions. We determined a Michaelis-Menten constant of about 0.3 micrograms/ml from the data of two publications and from our own investigations. From the steady-state concentrations we calculated the necessary amount for the realization of a desired concentration of 1.0 micrograms/ml. The interindividual differences and intraindividual changes of the pharmacokinetics were high (median: 6.9 mg/kg/d (2.7-17.1), n = 110). The intraindividual stability of the pharmacokinetics of repeatedly investigated patients (n = 20, individual time of observation: 4 to 296 days, median: 30 d) depended on various pathophysiological factors of influence. The individual duration of pharmacokinetically stable periods in relation to the respective observation time ranged between 0 and 100% (median: 75%, n = 23). In the initial days of treatment the course of itraconazole concentrations in repeatedly investigated patients (n = 6) was not uniform. Under constant dosage only one patient showed the increase in concentrations described in the literature during the first week of treatment. In this period of treatment probably three pharmacokinetic processes overlap one another: the establishment of the steady state, and systematic changes as well as changes caused by pathophysiological factors of the underlying disease. The development of therapeutic drug monitoring (with the calculation of the needed dosages) was unproblematic with the use of standard procedures. Necessity and frequency of therapeutic drug monitoring depend on the accepted ranges of concentration during long-term therapy, on the expected deviation of the pharmacokinetics during the course of the basic illness of the individual patient and on potential drug interactions.
