The pharmacokinetics of ifosfamide given as short and long intravenous infusions in cancer patients.
1. We investigated the pharmacokinetics of ifosfamide 5 g m-2 given by two regimens. Six patients (one female), median age 55 (range 40-71) years, all with lung cancer received 5 g m-2 ifosfamide (median ifosfamide dose 8.95 g) as an intravenous infusion over 0.5 h with mesna. Four other cancer patients (all male) of median age 52.5 (range 23-72) years were studied on seven treatment occasions with 5 g m-2 ifosfamide (median ifosfamide dose 8.88 g) as a 24 h intravenous infusion with mesna. Plasma was assayed for ifosfamide by gas liquid chromatography and for alkylating activity by the nitrobenzylpyridine method. 2. After ifosfamide 5 g m-2 infused over 0.5 h, the decay of the plasma ifosfamide concentration was monoexponential with a median (range) t1/2,z of 5.4 h (3.6-10.4 h). The median clearance was 60 ml min-1 (47-104) and the median volume of distribution was 388 (329-783) ml kg-1. Plasma nitrobenzylpyridine alkylating activity showed a biexponential decay in four patients and a monoexponential decay in two, with a median AUC of 102 (24-177) nmol nor nitrogen mustard eq h ml-1. 3. When ifosfamide 5 g m-2 was given as a 24 h infusion, the decay of the plasma ifosfamide concentration was monoexponential, the median (range) t1/2,z was 4.5 (3.4-6.1), the median volume of distribution was 563 (292-818) ml kg-1 and the median clearance was 79 (59-116) ml min-1. Plasma nitrobenzylpyridine alkylating activity decayed monoexponentially and the median AUC was 49 (45-131) nmol nor nitrogen mustard eq ml-1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Lewis
L D
LD
Division of Clinical Pharmacology, United Medical School, Guy's Hospital, London.
Fitzgerald
D L
DL
Mohan
P
P
Thatcher
N
N
Harper
P G
PG
Rogers
H J
HJ
D000328:Adult; D000368:Aged; D000478:Alkylation; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011725:Pyridines
D011725:Pyridines; C008633:4-(4-nitrobenzyl)pyridine; D007069:Ifosfamide