PHARMACOKINETICS AND PHARMACODYNAMICS OF DOXORUBICIN IN PATIENTS WITHSMALL-CELL LUNG-CANCER

The pharmacokinetics and pharmacodynamics of doxorubicin and its metab olite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years ) patients with small cell lung cancer after a 1-hour intravenous infu sion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum conc entrations were sampled to 48 hours after dosing. Wide interpatient va riability was observed for all pharmacokinetic parameters with coeffic ients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62%, 65%, and 65%, respectively. Four p atients with impaired liver function showed a significant (p < 0.05) d ecrease in clearance (239 versus 666 ml/min/m2) and increases in AUC ( 4610 versus 1834 ng . hr/ml) and elimination half-life (49.3 versus 25 .6 hours) compared with patients with normal hepatic function. A signi ficant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposu re and surviving factor of white blood cells or platelets. These findi ngs show the important relationship between systemic exposure of doxor ubicin and the degree of myelosuppression in patients with small cell lung cancer.