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“Vitamin B12 was administered intravenously and transdermally to eight surgical patients to determine the systemic bioavailability and rate of absorption of the transdermally administered drug. Serum vitamin B concentrations reached a plateau approximately 4-8 h after placement of the transdermal vitamin delivery system. This plateau was maintained until removal of the system at 6 h. The decline in serum vitamin B12 concentrations after removal of the transdermal system had a terminal half-life of 17.0 +/- 2.3 h (mean +/- SD), considerably longer than the terminal elimination half-life seen after intravenous administration of vitamin B12 in the same patients (6.1 +/- 2.0 h). The rate of Vitamin B12 absorption, predicted to be 100 micrograms/h from in vitro data, appeared to be relatively constant during a period starting 4-8 h after placement of the transdermal system until removal of the system at 8h. The rate of absorption during this period was 91.7 +/- 25.7 micrograms/h. After removal of the transdermal vitamin B12 delivery system, absorption continued at a declining rate. This indicates that the long terminal half-life of serum Vitamin B12 concentrations after transdermal system removal is due to continued slow absorption of B12, probably from a cutaneous depot of drug at the site of prior transdermal system placement. At the time of removal of the transdermal vitamin B12 system, 1.07 +/- 0.43 mg of drug remained in this depot. Systemic vitamin B12 bioavailability was found to be 0.92 +/- 0.33, with no evidence of significant cutaneous metabolism or degradation by the skin's bacterial flora. The transdermal administration of vitamin B12 produces relatively constant serum concentrations for significant periods of time.”