Comparative bioavailability of metoprolol tartrate after oral and transdermal administration in healthy male volunteers.

BACKGROUND AND OBJECTIVE

Transdermal drug delivery systems (TDDSs) of metoprolol tartrate have been previously prepared and evaluated in vitro and in vivo in an animal model. This study compares the bioavailability of metoprolol tartrate from a TDDS with that from a conventional marketed tablet in healthy human volunteers.

METHODS

This was an open-label, balanced randomised, two-treatment, two-period crossover study with a washout period of 1 week. Volunteers were randomised (by means of a SAS software-generated randomisation schedule) to have a TDDS applied to their chest for 48 hours or to receive a 100 mg conventional marketed tablet of metoprolol tartrate in period I. In period II, the volunteers received the other dosage form. Blood samples were collected through an indwelling cannula placed in the forearm vein of each subject. Metoprolol tartrate concentrations were quantified in plasma samples by a validated high-performance liquid chromatography method.

RESULTS

A 3-fold improvement in bioavailability was observed with the TDDS form over oral therapy as shown by the extent of absorption indicated by the mean area under the concentration-time curve from time zero to time t values for tablets (451.98 ng x h/mL) and TDDS (1552.66 ng x h/mL). Although the maximum plasma concentration was higher for the tablet form than the TDDS (77.67 +/- 23.33 vs 51.16 +/- 16.61 ng/mL), the variable absorption profile, which is a characteristic feature of oral therapy, was quite evident. Plasma metoprolol tartrate concentrations plummeted to therapeutically ineffective concentrations as early as 8 hours following oral administration.

CONCLUSION

The TDDS developed in our laboratory produced therapeutically effective plasma concentrations for up to 48 hours, with a minimum of 26.09 ng/mL and a maximum of 76.70 ng/mL, which is in good agreement with the therapeutic range (20-100 ng/mL) of metoprolol tartrate. It could be concluded that the TDDS meets the intended goal of 2-day management of hypertension with application of a single patch, obviating the inconvenience of frequent administration and thus improving patient compliance.