Clinical pharmacokinetics of ifosfamide in combination with N-acetylcysteine.
The pharmacokinetics of ifosfamide were studied in 20 patients with soft tissue and bone sarcomas. Drug was administered as a 30-60 min i.v. infusion at 1.2 or 2.0 mg/m2/day for five consecutive days. Some patients also received 1.5 g/m2 of N-acetylcysteine (NAC) administered 3 times per day during the course of therapy. NAC had no effect on ifosfamide pharmacokinetics. There were significant differences in plasma half-life, area under the concentration-time curve and plasma clearance on day 1 versus day 5 of ifosfamide administration. Myelosuppression and granulocytopenia correlated better with day 1 versus day 5 ifosfamide pharmacokinetics suggesting that the alteration of ifosfamide pharmacology with multiple dosing has a significant effect on drug activity.
Benvenuto
J A
JA
Department of Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston 77030.
Ayele
W
W
Legha
S S
SS
Raber
M N
MN
Nicaise
C
C
Newman
R A
RA
D000111:Acetylcysteine / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000380:Agranulocytosis / Q000188:drug therapy; D001853:Bone Marrow / Q000187:drug effects; D006801:Humans; D007069:Ifosfamide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012509:Sarcoma / Q000188:drug therapy*
D007069:Ifosfamide; D000111:Acetylcysteine