Clinical pharmacokinetics of amonafide (NSC 308847) in 62 patients.
Amonafide (A) demonstrates dose-related increases in area under the curve (AUC) and Cmax values. Total body clearance for A (ranging from 44.2 to 53.8 L/hr/m2) is relatively constant within the dosing range of this study. The dose-related increase of AUC was also observed for the two identified metabolites, acetylamonafide (AA) and noramonafide (NA). A and NA plasma data could be described by a four-compartmental model (two compartments for A, one compartment each for NA and AA). The fitting for NA was poor owing to its low plasma concentration. The terminal half-lives for A, NA, and AA were in the range of 3-6 hr. No cumulative accumulation of parent compound or metabolites was detected after daily administration, The concentrations of A, NA, and AA 24 hr after dosing were either below or very close to the quantitative limits of the assay. Polymorphic disposition of A was confirmed by a frequency distribution of AUC value versus dose plot.
Kreis
W
W
North Shore University Hospital, Cornell University Medical College, Manhasset, New York 11030, USA.
Chan
K
K
Budman
D R
DR
Allen
S L
SL
Fusco
D
D
Mittelman
A
A
Hock
K
K
Akerman
S
S
Calabro
A
A
Puccio
C
C
Spigelman
M
M
D000225:Adenine; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007094:Imides / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007546:Isoquinolines / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008433:Mathematics; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D053644:Naphthalimides; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D063065:Organophosphonates; D011110:Polymorphism, Genetic
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D063065:Organophosphonates; C037020:amonafide; D000225:Adenine