Population pharmacokinetics in phase I drug development: a phase I study of PK1 in patients with solid tumours.

摘要: Doxorubicin pharmacokinetics were determined in 33 patients with solid tumours who received intravenous doses of 20-320 mg m(-2) HPMA copolymer bound doxorubicin (PK1) a phase I study. Since assay constraints limited the data at lower doses, conventional analysis was not feasible and 'population approach' used. Bound concentrations best described by biexponential model further analyses revealed small influence dose or weight on V1 but no identifiable effects age, body surface area, renal hepatic function. The final was: clearance (Q) 0.194 h(-1); central compartment volume (V1) 4.48 x (1+0.00074 (mg)) I; peripheral (V2) 7.94 intercompartmental 0.685 h(-1). Distribution elimination half-lives had median estimates 2.7 h 49 respectively. Free present most sampling times around 1000 than values. Data using following parameters estimated: apparent 180 h-(-1); (I) 1450 (1+0.0013 (mg)), V2 21 300 (1-0.0013 (1+2.95 height (m)) Q 6950 0.13 85