Pharmacokinetics and dissolution of raltegravir

28 29 The pharmacokinetics of raltegravir (RAL) in HIV patients is characterised by high 30 inter/intra-patient variability. We investigated the potential contribution of the drug 31 pharmaceutical formulation on RAL pharmacokinetics. 32 We firstly compared in vivo the pharmacokinetics of RAL from 67 patients in which 33 the drug was administered by swallowing the intact tablet with those obtained from 13 34 HIV-infected patients that chewed the RAL tablet due to swallowing difficulties. 35 Subsequently, we evaluated in vitro the dissolution of RAL tablets under different 36 conditions. 37 In the in vivo study we found that patients given RAL by chewing the tablets presented 38 pharmacokinetic profiles characterised by significantly higher RAL absorption 39 compared with patients receiving the drug by swallowing. The in vitro studies showed 40 that when the whole tablets were exposed to an acidic medium the release of RAL was 41 very low, whereas when crushed the profiles presented significantly higher 42 concentrations of RAL. Crushed tablets tested in water or in a pH 6.8 buffer exhibited 43 prompt and complete dissolution of RAL. 44 HIV-infected patients receiving RAL by chewing the tablet showed higher drug 45 absorption and reduced pharmacokinetic variability compared with patients swallowing 46 the intact tablet. This is related to problems in the tablet disintegration and to erratic 47 drug absorption. The amelioration of the RAL pharmaceutical formulation could 48 improve drug pharmacokinetics. 49 50 on July 0, 2017 by gest httpaac.asm .rg/ D ow nladed fom Pharmacokinetics and dissolution of raltegravir