acceptable as a PET ligand.  Following the baseline PET study, each subject received a single oral dose of 150 mg sustained-release bupropion HCl administered every 24 hours in the morning for 3 consecutive days (Days 1-3) followed by 7-1/2 days of 150 mg sustained-release bupropion HCl given every 12 hours (Days 4-10).  Subject reported to the outpatient clinic of pre-dose blood sampling for pharmacokinetic (PK) analysis on the mornings of Days 8-10.  Subjects were admitted to the study unit on the evening of Day 10 and remained there until the morning of Day 12.  On the morning of Day 11, following a fast of at least 8 hours, each subject receiving 150 mg sustained-release bupropion HCl (12 hours following the previous evening dose).  Blood sampling was performed at fixed times following the morning dose on Day 11.  At 3, 12, and 24 hours following the dose on Day 11, subjects were injected with the PET tracer ¹¹C-ßCIT-FE and scanning was conducted.

 

Blood samples were collected at fixed times.  Samples were collected on Day 8-10 just prior to the morning dose.  On Day 11, samples were collected at 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 8.0, 12.0, 12.75, 13.5, and 24, 24.75, and 25.5 hours post-drug administration.  Details of the storage conditions were not described.

 

A single blood sample was also collected for pharmacogenetic assessments that included NET and DAT transporters, CYP2B6, and UDP glucuronosyl transferases.

 

ASSAY:

Details of the analytical methods and assay performance were not provided.  According to the Sponsor, samples were analyzed for bupropion, hydroxybupropion and composite of erythrohydrobupropion and threohydrobupropion using a validated LC/MS/MS assay.  The lower limit of quantification was [blacked out] for bupropion, [blacked out] for hydroxybupropion and [blacked out] for erythro/threohydrobupropion.  Samples were also analyzed for the hydroxybupropion enantiomers, [blacked out] (the (+)-enatiomer) and [blacked out] using a non-GLP LC/MSMS assay for which the lower limit of quantification was [blacked out].

 

 

RESULTS:

 

Demographics:

 

Six male Caucasians subjects were enrolled and completed the study.  The mean age was 30.7 and the age range was 23-39 years of age.  The (mean ± SD) was 80.0 ± 14.5 kg.

 

Pharmacokinetics

 

Pharmacokinetic parameters were determined using noncompartmental analysis.  The pertinent pharmacokinetic parameters, as provided by the Sponsor, are shown in Table 2 below.

 

 

63

 

 

 

 

 

 

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