Two calibration curves and duplicate QC samples (at 4 concentration levels) were analyzed with each batch of study samples.  At least 6 out of 8 QC samples were within [blacked out] of their respective nominal value, except for 1 run for hydroxybupropion in which 5 out of 8 samples (62.5%) were within [blacked out] of the nominal value.  Study samples were stored at -70°C.  Samples were analyzed within the period for which the samples are stable at -70°C.  The performance of the assays for all analytes is considered acceptable.

 

RESULTS:

 

Demographics

 

Thirty-six (26 males and 10 females) were enrolled in the study and received investigation product.  The mean age of the subjects was 31.4 years of age, and the range was 21 to 46 years old.  Thirty-two subjects completed the study and were eligible for pharmacokinetic analysis.  Two subjects withdrew due to adverse events during Period 1, 1 subject withdrew due to difficult blood draws, and 1 subject withdrew for personal reasons.  An additional subject was not included in the pharmacokinetic analysis population due to vomiting.  The demographics of the thirty-one subjects included in the pharmacokinetic analysis population are shown below.

 

Table 4.  Demographics of Subjects Included in the Pharmacokinetic Analysis Population

Mean Age (Range)	Gender	Weight (mean ± SD)	Race
31.8 (21-46)	23 males 8 females	75.1 ± 9.4 kg (n=31) 78.8 ± 6.9 kg (male) 64.4 ± 7.1 kg (female)	Asian           2 Black           6 Caucasian    23

 

Pharmacokinetics

 

In addition to evaluation of the pharmacokinetics of the parent compound and its active metabolites, the pharmacological activity-weighted composite (PAWC) was also evaluated.  The PAWC was calculated by dividing the measured concentrations by the respective molecular weight of each moiety followed by multiplication by the previously determined relative potency in an animal model of antidepressant activity.  The sum of the resultant values represents the PAWC.

 

Pharmacokinetic parameters were determined using noncompartmental analysis.  The plasma concentration time course and the pertinent pharmacokinetic parameters for bupropion, its metabolites, and the PAWC are shown in Figure 1 and Tables 5 and 6, below.

 

 

69

 

 

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