The uptake and metabolism of ginsenoside Rh2 (Rh2) by B16 melanoma cells were studied. In a medium containing 2% fetal calf serum, the uptake of Rh2 reached a maximum of 3 nmol/10(6) cells at 3-6 h after Rh2 (12.5 microM) was added, but gradually decreased to 0.8 nmol/10(6) cells. In these cells, protopanaxadiol (PPD), which is an aglycon of Rh2, increased inversely with the decrease in Rh2 as a result of deglycosylation by the cells. When PPD (8 microM) was added to the medium, the uptake reached a plateau of 2.4 nmol/10(6) cells, within 0.5 h. The association constant of Rh2 (1.74 +/- 1.08 x 10(6) M-1) for bovine serum albumin (BSA) was significantly higher than that of PPD (9.90 +/- 1.10 x 10(4) M-1). In a serum-free medium, both Rh2 and PPD were incorporated within 1.5 h. The uptake rate constant of Rh2 (1.20 +/- 0.20 h-1) was not significantly different from that of PPD (1.02 +/- 0.15 h-1), but the release rate constant of PPD (2.12 +/- 0.38 h-1) was significantly lower than that of Rh2 (3.03 +/- 0.57 h-1). These differences in affinity for BSA and the release rate constants were thought to be the cause of the difference in uptake kinetics between these drugs. The effects of Rh2 and PPD on the cells were identical, and there was no difference in the lag periods before the appearance of their effects, despite their differing rates of uptake.(ABSTRACT TRUNCATED AT 250 WORDS)