All 12 subjects tolerated their dose(s) well without any grade 2 toxicity or adjustment of dose. Six subjects experienced mild, transient sypmpoms, primarily gastrointestinal in nature. These events were not dose-related. All subjects expericned a dose-related elevation in white blood cell counts, ranging from 1.5 to 3.2 times baseline values, which returned to baseline by 24 hours after dosing. In non-compartmental pharmacokinetic studies, AMD-3100 demonstrated dose proportionality for Cmax and AUC over the entire dose range. A5t the highest dose level (80mg/kg), the medial Cmax was 515 ng/ml (range:470-521) and AUCinf was 1044 ng-hours/ml (range:980-1403). The median systemic bioavailability of the subcutaneous dose in five volunteers was 87% (range 67-106%). No drug was detectable in the blood following oral doses up to 160 mg/kg. A compartmental analysis of AMD-3100 data best fit a three compatment pharmacokinetic model, but this was marginally better than the simpler 2-compartment model. Using the 2-compartment model, the pharmacokinetic parameter estimates in the 2 higher dose cohorts (where terminal elimination was more reliably estimated) were as follows (median (range)): volume of distribution 0.34 L/kg (0.27-0.36), clearance 1.30 L/hr (0.97-1.34), elimination half-life 3.6 hours (3.5-4.9). rn
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