title: Pharmacokinetic interaction study combining lapatinib with vorinostat in rats.
abstract: BACKGROUND
  Because lapatinib and vorinostat [suberoylanilide hydroxamic acid (SAHA)] are both new anticancer drugs, interactions between SAHA and lapatinib remain unclear. This study examines pharmacokinetic interactions in simultaneous oral administration of SAHA and lapatinib to rats.
  
  
  METHODS
  Twenty-four rats were divided randomly into 3 groups: a lapatinib group (lapatinib 25 mg/kg, n = 8), a SAHA group (SAHA 25 mg/kg, n = 8), and a coadministration group (SAHA 25 mg/kg and lapatinib 25 mg/kg, n = 8). Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, the concentrations of lapatinib and SAHA were determined in the plasma of the test rats.
  
  
  RESULTS
  Statistically significant pharmacokinetic differences appeared for lapatinib levels between the lapatinib and the coadministration group. When lapatinib was coadministered with SAHA, the AUC0-t decreased from 39,816.6 to 23,712.8 ng/ml ∙ h (p < 0.05), while the mean residence time (MRT)0-t increased from 7.0 to 10.3 h (p < 0.05) and t1/2 increased from 3.5 to 6.4 h (p < 0.05). Between the SAHA levels for the SAHA group and those for the coadministration group, there appeared to be no statistically significant differences.
  
  
  CONCLUSIONS
  The resulting data indicate that, when administered together, lapatinib does not influence the pharmacokinetic profile of SAHA in rats, while, in contrast, SAHA influences the pharmacokinetic profile of lapatinib.
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Lin
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wu
authors.forename: Huilong
authors.initials: H
authors.lastname: Zou
authors.forename: Peiwu
authors.initials: P
authors.lastname: Geng
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006877:Hydroxamic Acids / Q000097:blood / Q000493:pharmacokinetics*; D000077341:Lapatinib; D008297:Male; D011799:Quinazolines / Q000097:blood / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D011799:Quinazolines; D000077341:Lapatinib; D000077337:Vorinostat