Green Tea Extract Decreases the Systemic Exposure of Pazopanib in Healthy Participants

Green tea catechins modulate the activity of key drug pharmacokinetic determinants and consequently, concomitant consumption of green tea can significantly alter systemic drug exposure. This study aimed to investigate the influence of concomitant green tea catechin consumption on the pharmacokinetics of pazopanib, a tyrosine kinase inhibitor used in the treatment of advanced renal cell carcinoma and advanced soft tissue sarcoma. An open‐label, single‐dose, fixed‐sequence pharmacokinetic study in 15 healthy participants was conducted. Participants were administered a 200 mg pazopanib tablet on Day 1 (Control Period) and Day 15, and an 833 mg green tea extract tablet once daily on Days 10–18 (Green Tea Extract Period). Fourteen healthy participants completed the study. Concomitant green tea extract consumption significantly reduced pazopanib oral systemic exposure. The geometric mean ratios (Green Tea Extract/Control) for pazopanib maximum plasma concentration ( C max ), area under the plasma concentration–time curve (AUC) from time 0 to last quantifiable timepoint (AUC 0‐t ), AUC extrapolated to infinity (AUC 0‐∞ ) and half‐life ( t 1/2 ) were 0.44 (90% CI: 0.30–0.64, n = 14), 0.53 (90% CI: 0.41–0.68, n = 13), 0.57 (90% CI: 0.44–0.74, n = 13) and 1.12 (90% CI: 1.05–1.20, n = 13), respectively. Median pazopanib time of C max ( T max ) was slightly shorter in the Control Period (4.0 h) than the Green Tea Extract Period (4.5 h, P < 0.01, n = 14). Given the established concentration–response relationships for pazopanib anticancer effects, decreases in pazopanib systemic exposure with green tea catechin consumption may be clinically important.