Multiple dose pharmacokinetics of an oral solution of itraconazole in patients receiving chemotherapy for acute myeloid leukaemia.
The multiple dose pharmacokinetics of a solution of itraconazole given orally were measured in an open study of 20 patients undergoing remission induction chemotherapy for acute myeloid leukaemia. Patients were given itraconazole 5 mg/kg od, 2.5 mg/kg bd, 2.5 mg/kg od or 1.25 mg/kg bd. The mean daily dose of itraconazole was 407 mg for patients receiving 5 mg/kg/day and 148 mg in patients receiving 2.5 mg/kg/day. Mean concentrations of 493 and 495 micrograms/L were achieved on day 8 in patients who received 5 mg/kg/d od or 2.5 mg/kg bd itraconazole respectively. However, mean concentrations were significantly lower for those who received 2.5 mg/kg od itraconazole being 110 micrograms/L on day 8. Mean areas under the serum-concentration time curves were also markedly higher in patients receiving 5 mg/kg/day than in those receiving 2.5 mg/kg/day itraconazole and were 22,382 and 5615 micrograms.h/L on day 15 respectively. These findings suggest that the serum concentrations attained with an oral solution of 5 mg/kg itraconazole either once daily or in two divided doses are suitable for antifungal prophylaxis in patients receiving chemotherapy for acute myeloid leukaemia.
Prentice
A G
AG
Department of Haematology, Derriford Hospital, Plymouth, UK.
Warnock
D W
DW
Johnson
S A
SA
Taylor
P C
PC
Oliver
D A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D017964:Itraconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D017964:Itraconazole