title: Study of pharmacokinetic interaction of paroxetine and roxithromycin on bencycloquidium bromide in healthy subjects.
abstract: OBJECTIVE
  The aim of this study was to investigate the potential drug-drug interaction between Bencycloquidium bromide (BCQB) and paroxetine, and between BCQB and roxithromycin.
  
  
  METHODS
  Two studies were conducted on healthy male Chinese volunteers. Study A was an open-label, two-period, one-sequence crossover study (n=21). Each participant received a single nasal spray dose of BCQB 180μg on day 1. After a 7-day wash-out period, subjects received 20mg of paroxetine from day 8 to 17, and were co-administered 20mg of paroxetine and BCQB 180μg on day 18. In study B, participants (n=12) were randomly assigned to two groups. In period I, group A received BCQB 180μg on day 1, followed by the same dose four times daily from day 4 to 10, then, on day 11 a single dose of 150mg roxithromycin with BCQB 180μg were co-administered. In parallel, group B received a single dose of roxithromycin 150mg on day 1, followed by 300mg of roxithromycin from day 4 to 10, then, on day 11 a single dose of BCQB 180μg with roxithromycin 300mg were co-administered. After a wash-out time of 7days the respective treatments of each group (A and B) were swapped in period II. Blood samples were collected for pharmacokinetic analysis. Statistical comparison of pharmacokinetic parameters was performed to identify a possible drug interaction between treatments. Tolerability was evaluated by recording adverse events.
  
  
  RESULTS
  Study A: Geometric mean AUC0-36 for BCQB alone and co-administered with paroxetine were 474.3 and 631.3pgh/ml, respectively. The geometric mean ratio (GMR) of AUC0-36 was 1.33 (1.13-1.46), 90% C.Is, and was out the predefined bioequivalence interval (90% C.Is, 0.80-1.25). Geometric mean Cmax were 187.0 and 181.2pg/ml. Study B: The GMR of AUC0-36 was 0.98 (0.90-1.07), 90% C.Is for BCQB, and the GMR of AUC0-72 was 0.98 (0.87-1.11), 90% C.Is for roxithromycin. Both GMRs were within the predefined bioequivalence interval (90% C.Is, 0.80-1.25). Other pharmacokinetic parameters were within the predefined interval. No serious adverse events were reported and no significant clinical changes were observed in laboratory test results, vital signs and ECGs in any of the studies. All treatments were well tolerated.
  
  
  CONCLUSIONS
  The co-administration of BCQB with paroxetine showed a moderate increase in BCQB exposure, but was not clinically relevant. Also, no drug interaction was found between BCQB and roxithromycin.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Janvier Engelbert
authors.initials: JE
authors.lastname: Agbokponto
authors.affiliation: Department of Clinical Pharmacology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: tayler22@tom.com.
authors.forename: Maozhi
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: dinglidl@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D017374:Paroxetine / Q000494:pharmacology*; D015575:Roxithromycin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D018727:Muscarinic Antagonists; C518439:bencycloquidium bromide; D015575:Roxithromycin; D017374:Paroxetine
keywords: Bencycloquidium bromide; Drug interaction; Paroxetine; Pharmacokinetics; Roxithromycin