Abstract
To determine the plasma concentrations and to clarify pharmacokinetic behavior from a pharmaceutical application viewpoint, indomethacin (IND) and its calcium salt (IND-Ca) in the form of gel ointments were applied singly and repeatedly to rat abdominal skin under occlusions. In order to describe the plasma IND concentration profile during repeated percutaneous administration, a highly simple pharmacokinetic model including a first-order absorption process with a lag time was applied. IND and IND-Ca were readily absorbed with a short lag time from IND-Ca ointment (1% as IND, 0.14 g/cm2, 3.0×1.2 cm area) containing Azone[○!R]. Even when the applied dose of IND-Ca ointment was decreased to one-fourth (1.0×1.0 cm area), the plasma IND concentrations were maintained above the effective levels for 24h. The use of the pharmacokinetic model was justified by good agreement with observed data obtained after repeated percutaneous application of ointments. Thus, the plasma IND concentration-time courses during repeated percutaneous administration can be predicted by using the model.
