Pharmacokinetics and safety of a 7-day administration of intravenous itraconazole followed by a 14-day administration of itraconazole oral solution in patients with hematologic malignancy.

The pharmacokinetics and safety of an intravenous hydroxypropyl-beta-cyclodextrin solution of itraconazole administered for 7 days followed by itraconazole oral solution administered at 200 mg once or twice daily for 14 days were assessed in 17 patients with hematologic malignancies. Steady-state plasma itraconazole concentrations were reached by 48 h after the start of intravenous treatment. The mean trough plasma itraconazole concentration at the end of the intravenous treatment was 0.54 +/- 0.20 microg/ml. This concentration was not maintained during once-daily oral treatment but increased further in the twice-daily treatment group, with a trough itraconazole concentration of 1.12 +/- 0.73 microg/ml at the end of oral treatment. As expected in the patient population studied, all patients experienced some adverse events (mainly gastrointestinal). Biochemical and hematologic abnormalities were frequent, but no consistent changes occurred. In conclusion, 7 days of intravenous treatment followed by 14 days of twice-daily oral treatment with itraconazole solution enables plasma itraconazole concentrations of at least 0.5 microg/ml to be reached rapidly and to be maintained. The regimen is well tolerated and has a good safety profile.

Kinetic evaluation of muscle damage during exercise by calculation of amount of creatine kinase released.

To quantify the extent of muscle alteration during prolonged exercise, the release rate of creatine kinase (CK) from striated muscle was measured in six horses during a rest period (6 h) and during three exercise tests (15, 30, and 60 km) at a constant speed of 200 m/min. CK clearance was measured after intravenous bolus administration (150 U/kg) of a CK solution obtained from horse muscle. The CK steady-state volume of distribution was 0.059 +/- 0.0215 l/kg, the terminal half-life was 123 +/- 28 min, and the plasma clearance was 0.36 +/- 0.10 ml.kg-1 x min-1. After an intramuscular CK administration, the CK systemic availability was 74.1 +/- 21.2% and the half time of absorption was 9.4 +/- 5.7 h, indicating a slow process for CK transit through the lymphatic system. The CK release rate was only significantly increased during the 60-km exercise test. The increase of CK plasma activity was observed after a delay of approximately 5 h and peaked after the end of the race; the estimated CK release rate was 9.92 +/- 2.62 U.kg-1 x h-1 over a mean duration period of 65.8 +/- 15.8 h. With the CK activity of horse striated muscle taken into account, a 60-km race released a quantity of CK corresponding to an equivalent of 18.8 +/- 4.3 g striated muscle. It is concluded that the equivalent amount of damaged muscle may be considered as negligible for a 60-km test and that only very high plasma CK activity levels (at least higher than 10,000 U/l) may provide some evidence of a myolysis.