product.  The % CV in the pharmacokinetic parameters ranged from (whited out) for bupropion, (whited out) for 306U73, 31-41% for 494U73, and (whited out) for 17U67.

 

A multiple dose bioequivalency study involving the highest SR tablet strength (150 mg) showed that the 150 mg SR tablet given every 12 hours is equivalent to the 100 mg IR tablet given every 6, 6, and 12 hours; each treatment was administered for 14 days: n-34.  For bupropion, AUC and Cmin were inside the confidence intervals of 80-125%, while Cmax was slightly outside (78-89%).  For the three active metabolites, and for the pharmacologic activity weighted composite (PAWC), the pharmacokinetic parameters were within the 80-125% range.  The fluctuation index for bupropion was about 15% lower for the SR tablets than for the IR tablets.  The fluctuation indices for 306U73, 494U73, 17U67, and the PAWC for the SR tablet ranged from 95 to 102% of the respective index of IR tablet.  In general, the adverse events were less frequent with the DR tablet than with the IR tablet.

 

Dosage strength equivalency was seen between the 50 mg SR, 100 mg SR, and the 150 mg SR tablets when equal single oral doses of 300 mg were administered; n-36.

 

Food appears to have minimal effect on the SR tablet as indicated in a single-dose study involving the highest strength – 150 mg; (bupropion AUC fed ↑ by 16%; Cmax ↑ by 11%, 494U73: AUC fed ↑ by 11%); n=24.

 

in vitro / in vivo correlation attempts indicate that a good correlation exists when 0.1N hydrochloric acid, water, and pH 4.5 phosphate buffer are used as the dissolution media (slope of the line of mean % absorbed versus mean % released was close to unity).

 

The Division of Biopharmaceutics recommends the following dissolution specification for all strengths of WELLBUTRIN® SR tablets (50, 100, and 150 mg):

 

 

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