Effect of body weight on the pharmacokinetics of cyclophosphamide in breast cancer patients

Abstract

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.

Urinary excretion and pharmacokinetics of acrolein and its parent drug cyclophosphamide in bone marrow transplant patients

“…13,14 While the ␤-phase half-life (t 1/2␤ ) of CP obtained in this study is consistent with values reported previously, [15][16][17][18][19] the value of the ␤-phase volume of distribution (V t ) in this study was somewhat larger than those previously reported for the volume of distribution in humans, 20 which resulted in a markedly larger total clearance (CL) of CP as compared to that reported by other investigators. 16,19,21 It should be noted that when a similarly higher dose of CP was used, the volume of distribution at steady state (V ss ) (ie, 30.20 l) 12 was somewhat close to the value of V ss calculated in this study (ie 39.23 l). The mean fraction of CP dose excreted in urine (f u ) in the unchanged form was 14.05% which compares favorably with previously reported values for this parameter (ie 10.78%, 12 17% 13 ) after intravenous infusion of high doses of CP, but a large variation has been observed by other investigators 22 which is also the case in the present study.…”

Population pharmacokinetics of cyclophosphamide in patients with thalassemia major undergoing HSCT

“…Body weight as a factor influencing CY PK has been reported in patients with breast cancer receiving CY therapy. 39,40 In addition, patients with CYP2C9*2 variant genotype showed significantly lower CY elimination and higher AUC. Recognizing the factors that influence CY and HCY PK in this pediatric population might help in designing individualization of therapy.…”

Impact of pretransplant body mass index on the clinical outcome after allogeneic hematopoietic SCT

“…It was reported that there was a correlation between total body weight and plasma half-life of CY, which means that the concentration of CY is higher in obese patients compared with the normal weight patients. 31 Such changes in the metabolism of chemotherapeutic drugs might affect the risk of relapse and NRM in the setting of allogeneic HSCT. An intervention that may improve the outcome is the amelioration of body weight loss before allogeneic HSCT.…”