Novel paclitaxel formulations for oral application: a phase I pharmacokinetic study in patients with solid tumours
To explore the pharmacokinetics (PKs) of paclitaxel and two major metabolites after three single oral administrations of a novel drinking solution and two capsule formulations in combination with cyclosporin A (CsA) in patients with advanced cancer. Moreover, the tolerability and safety of the formulations was studied. In addition, single nucleotide polymorphisms in the multidrug resistance (MDR1) gene were determined. Ten patients were enrolled and randomized to receive CsA 10 mg/kg followed by oral paclitaxel 180 mg given as (1) drinking solution (formulation 1), (2) capsule formulation 2B, and (3) capsule formulation 2C on day 1, 8, or 15. The median C max of paclitaxel was 0.42 (0.23–0.96), 0.48 (0.08–0.59), and 0.39 (0.11–1.03) μg/ml and the area under the plasma concentration–time curve was 2.83 (1.69–5.12), 2.01 (1.57–3.04), and 2.67 (1.05–3.61) μg h/ml following administration of formulations 1, 2B, and 2C, respectively. The novel formulations were tolerated after single oral dose without causing relevant gastrointestinal or haematological toxicity. The PK and metabolism of paclitaxel were comparable between the oral formulations co-administered with CsA.