Effect of body weight on the pharmacokinetics of cyclophosphamide in breast cancer patients.
Cyclophosphamide pharmacokinetics have been studied in 16 female patients with advanced breast cancer. The group included 7 patients who were greater than 20%, less than or equal to 30% over ideal body weight and 5 patients who were greater than 30% over ideal body weight. Cyclophosphamide plasma elimination half-lives ranged between 152 and 984 min (mean 457 min), the apparent volume of distribution between 19.1 and 62.3 1 (mean 36.1 1), and plasma clearance between 25.9 and 166.6 ml/min (mean 69.5 ml/min). There was a significant positive correlation (r = 0.624, P = 0.010) between body weight and plasma elimination half-life, and a significant negative correlation between body weight and cyclophosphamide clearance when normalized to body surface area (r = 0.578, P = 0.019) or normalized to ideal body weight (r = 0.531, P = 0.0345). The apparent volume of distribution did not correlate with body weight. The results show that cyclophosphamide disposition is altered in patients with increased body weight.
Powis
G
G
Department of Pharmacology, Mayo Clinic & Foundation, Rochester, Minnesota 55905.
Reece
P
P
Ahmann
D L
DL
Ingle
J N
JN
D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001835:Body Weight; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D009765:Obesity / Q000150:complications / Q000378:metabolism; D011241:Prednisone / Q000008:administration & dosage; D011897:Random Allocation
D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D011241:Prednisone