Novel paclitaxel formulations for oral application: a phase I pharmacokinetic study in patients with solid tumours.

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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) microg/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) mug 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.

CONCLUSIONS:

The PK and metabolism of paclitaxel were comparable between the oral formulations co-administered with CsA.

• Authors: S A Veltkamp, H Rosing, A D R Huitema, M R Fetell, A Nol, J H Beijnen, J H M Schellens
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 60 Issue 5 Pg. 635-42 (Oct 2007) ISSN: 0344-5704 [Print] Germany
• PMID: 17205304 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Capsules
• Cyclosporine
• Paclitaxel

Topics

• Administration, Oral
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Antineoplastic Combined Chemotherapy Protocols
• Capsules
• Chemistry, Pharmaceutical
• Cyclosporine (administration & dosage)
• Drinking
• Drug Administration Schedule
• Female
• Humans
• Infant
• Infant, Newborn
• Male
• Neoplasms (drug therapy)
• Paclitaxel (administration & dosage, adverse effects, chemistry, pharmacokinetics)