|Comparison of the Pharmacokinetics of Raltegravir Given at 400 mg Bid by Swallowing versus 800 mg qd by Chewing in Healthy Volunteers: A Randomized, Open-label, Two-period Cross-over Phase 1 Study|| |
|D. Cattaneo1, M.V. Cossu1, S. Fucile1, L. Testa1, P. Meraviglia2, S. Landonio2, M. Galli2, G. Rizzardini2, E.I. Clementi1, A. Riva2, A. Capetti2, C. Gervasoni2|
|1L. Sacco University Hospital, Unit of Clinical Pharmacology, Milan, Italy, 2L. Sacco University Hospital, Department of Infectious Diseases, Milan, Italy|
|Objectives: The pharmacokinetics of raltegravir (RAL) is characterized by high inter- and intra-patient variability probably related to inappropriate disintegration of the tablets in the gastric environment leading to erratic drug release. We compared the pharmacokinetic of two doses of RAL given at 400 mg every 12h by swallowing versus one dose of 800 mg by chewing the tablets in healthy volunteers. |
Methods: Randomized, open-label, two period cross-over study in 12 healthy volunteers. Intensive pharmacokinetic analyses were performed. RAL plasma concentrations were analyzed by a chromatographic method coupled with mass spectrometry.
Results: Subjects taking RAL by chewing the tablets presented regular pharmacokinetic profiles, characterized by single sharp drug peak (Figure) and significantly higher drug exposure (RAL AUC0-24: 40722 ± 14843 vs. 21753 ± 12229 ng*h/mL, p< 0.0001) compared with those taking the drug by swallowing the whole tablets, with no difference in the minimum RAL concentrations (RAL Cmin: 36 ± 23 vs. 43 ± 23 ng/mL, p=0.298). Large inter-individual variability in all the RAL pharmacokinetic parameters was observed in subjects given RAL by swallowing the tablets. This variability was, however, reduced by 20 to 1500% when the same subjects were given RAL at 800 mg by chewing the tablets.
Conclusion: Healthy subjects taking RAL by chewing the tablets have significantly higher drug absorption and reduced pharmacokinetic variability compared with those taking the drug by swallowing. No differences were observed in the minimum RAL concentrations. RAL at 800 mg/once daily by chewing the tablets may represent a novel therapeutic option for the treatment of HIV patients able to improve drug disposition and patients' compliance.
Pharm.D Ph.D Dario Cattaneo , L. Sacco University Hospital , Milan , Italy
Assigned in sessions:
17.10.2013, 12:00-14:00, Poster Session, Poster Session 1, Exhibition
18.10.2013, 12:00-14:00, Poster Session, Poster Session 2, Exhibition