Abstract
Purpose: 9-Aminocamptothecin (9-AC) is a topoisomerase I inhibitor with high antitumor activity but poor solubility in conventional vehicles. The purpose of this study was to evaluate the toxicities and pharmacokinetics of a colloidal dispersion (CD) formulation of 9-AC when administered orally on a 5 days per week every 2 weeks schedule. Method: This formulation, which was developed for intravenous administration, was orally administered in 20 ml orange juice. A group of 16 cancer patients were treated at doses of 0.2- 0.68 mg/m2 daily. Results: Grade 1-2 nausea (n = 9) was common, usually occurring during the last 2 days of dosing. No objective responses or cumulative toxicities were observed. Pharmacokinetic analysis of total 9-AC showed highly variable apparent oral 9-AC clearance and half-life. There was marked interpatient variability at each dose level in the 9-AC AUC and C(max), and these parameters:showed a poor correlation with dose (r2 = 0.07 and 0.38, respectively). Conclusions: We conclude that this formulation is not suitable for further clinical development because of poor bioavailability and highly variable and/or saturable absorption or elimination. Another formulation developed for oral administration is under study elsewhere.
Original language | English (US) |
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Pages (from-to) | 84-87 |
Number of pages | 4 |
Journal | Cancer Chemotherapy and Pharmacology |
Volume | 42 |
Issue number | 1 |
DOIs | |
State | Published - 1998 |
Externally published | Yes |
Keywords
- 9-Aminocamptothecin
- CD formulation
- Oral
- Pharmacokinetic
- Phase I
- Topoisomerase inhibitor
ASJC Scopus subject areas
- Oncology
- Toxicology
- Pharmacology
- Cancer Research
- Pharmacology (medical)