Pharmacokinetic linearity of i.v. vinorelbine from an intra-patient dose escalation study design.

摘要: As pharmacokinetics represents a bridge between pharmacological concentrations and clinical regimens, the pharmacokinetic exploration of therapeutic dose range is major outcome. This study was aimed at assessing linearity i.v. vinorelbine through an open design with intra-patient escalation (3 doses/group). Three groups six patients received either 20–25–30 mg/m2; or 25–30–35 30–35–40 mg/m2. The inclusion criteria were: histologically confirmed tumour least one assessable target lesion, age 25–75 years, WHO PS ≤2, normal haematology biochemistry, life expectancy ≥3 months. evaluated in both whole blood plasma over 120 h. Twenty-six were recruited 18 evaluable for pharmacokinetics. toxicity consisted grade ≤3 leucopenia neutropenia (<20% courses) two 4 constipation rapid recovery (2/54 courses). Compared to blood, demonstrated underestimate parameters. In drug total clearance about 0.6 l/h/kg, minor contribution renal clearance, steady state volume distribution close 13 elimination half-life 40 A up mg/m2, even 45 mg/m2 when pooling data from another study. pharmacokinetic–pharmacodynamic relationship evidenced on studies.