1999 Volume 14 Issue 1 Pages 11-15
The pharmacokinetics of tacrolimus (FK506) were studied in the male rat after a single dermal application of FK506 ointment over an application period of 24 hours. In the typical experiment, the amount of ointment applied was 100 mg per each rat, and application area was 10 cm2. The pharmacokinetic parameters estimated were maximal blood concentration (Cmax), time to reach Cmax (Tmax), and area under the blood concentration-time curve (AUC).
1. Blood concentrations of FK506 were determined after a single dermal application of FK506 ointment under the occlusive or non-occlusive dressing condition. After respective application of 0.5 and 0.1% FK506 ointment to the intact and damaged skin, Cmax and AUC values did not differ significantly between either dressing conditions. Blood concentrations of FK506 after a single dermal application of FK506 ointment to the damaged skin were much higher than those applied to the intact skin. The bioavailability of FK506 after application of 0.5% FK506 ointment to the intact skin was 5% and that to the damaged skin was 62%.
2. After a single dermal application of 0.03, 0.1 and 0.5% FK506 ointment to the intact skin, the Cmax and AUC values increased in proportion to the strength of the ointment. After a single dermal application of 0.3% FK506 ointment to 2.5, 5 and 10 cm2 of the intact skin, the Cmax and AUC values increased proportionally to the area of the skin. The Cmax and AUC values did not the differ significantly after single dermal application of 10, 30, 100 and 300 mg of 0.3% FK506 ointment to the intact skin.
