Lack of effect of aprepitant (APR) on the pharmacokinetics (PK) and safety of palonosetron (PALO)

Purpose PALO is a potent and highly selective 5-hydroxytryptamine3 receptor antagonist that has shown clinical efficacy for the prevention of both acute and delayed nausea and vomiting induced by moderately emetogenic chemotherapy. We evaluated the PK and safety of PALO with concomitant administration of APR, a neurokinin1 receptor antagonist, in healthy subjects. Methods This was an open-label, randomized, two-period crossover study in 12 subjects. Subjects received Treatment A: a single dose of PALO 0.25 mg IV and with a 14-day wash-out period Treatment B: APR 125 mg oral dose followed 30 minutes later by PALO 0.25 mg IV with daily oral dosing of APR 80 mg continued on days 2 and 3. Results Mean PK parameters of PALO are summarized below.(See Table) Conclusion PALO was well tolerated, with no clinically significant changes in vital signs or laboratory tests. These results indicate that the PK and safety of PALO were not altered with coadministration of APR. Clinical Pharmacology & Therapeutics (2004) 75, P78–P78; doi: 10.1016/j.clpt.2003.11.299 Table 1.  Cmax (ng/L) AUC(0-∞) (nghr/L) T1/2 (hr) CLp (mL/min) Vdss (L) † Geometric mean. $ %Ratio of geometric means. ¶ 90% Confidence Interval. ‡ p-Value for Treatment difference. PALO without APR 1700† 32900† 43.0 136 442 PALO with APR 1680† 33200† 40.0 130 411 98.6$ 101$       61.8, 157¶ 85.6, 119¶ 0.348‡ 0.735‡ 0.463‡