Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma.
Article Details
- CitationCopy to clipboard
Woo S, Gardner ER, Chen X, Ockers SB, Baum CE, Sissung TM, Price DK, Frye R, Piekarz RL, Bates SE, Figg WD
Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma.
Clin Cancer Res. 2009 Feb 15;15(4):1496-503. doi: 10.1158/1078-0432.CCR-08-1215.
- PubMed ID
- 19228751 [ View in PubMed]
- Abstract
PURPOSE: Romidepsin is a potent histone deacetylase inhibitor under clinical development. The objective of this study was to evaluate the effect of demographic, clinical, and pharmacogenetic covariates on the pharmacokinetics of romidepsin in patients with T-cell lymphoma. EXPERIMENTAL DESIGN: Pharmacokinetic assessment was done in 98 patients enrolled in a phase II study who received 14 or 18 mg/m2 of romidepsin as a 4-hour infusion on day 1 during their first treatment cycle. Population modeling was done using a nonlinear mixed effects modeling approach to explore the effects of polymorphic variations in CYP3A4, CYP3A5, SLCO1B3, and ABCB1, all of which encode genes thought to be involved in romidepsin disposition. RESULTS: A two-compartment model with linear kinetics adequately described the romidepsin disposition. Population clearance was 15.9 L/h with between-patient variability of 37%. ABCB1 2677G>T/A variant alleles tended toward a reduced clearance and lower volume of tissue distribution, but this was not supported by a statistical significance. Genetic variations in CYP3A4/5 and SCLO1B3 had no effect on the systemic exposure. CONCLUSION: The population pharmacokinetic analysis indicates moderate interindividual variability in romidepsin pharmacokinetics and no clinically relevant covariates associated with the unexplained pharmacokinetic variability of romidepsin in this population.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Romidepsin Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Romidepsin Cytochrome P450 3A5 Protein Humans UnknownSubstrateDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Romidepsin P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Romidepsin Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownInhibitorDetails