Transdermal delivery of ketorolac acid, a potent analgesic, through human skin in vitro and in vivo was evaluated. The following three transdermal solutions were selected to study the in vitro skin permeation rate of ketorolac acid: formulation A, isopropyl alcohol: water: isopropyl myristate (IPA/water/IPM; 11:7:1); formulation B, ethanol: propylene glycol:isopropyl myristate (ET/PG/IPM; 11:7:2); and formulation C, IPM/capmul (glyceryl mono- and dicaprylate; Monoctanoin). The permeation of ketorolac acid through cadaver skin from a saturated drug solution was evaluated at 32 degrees C with a modified Franz diffusion cell. The in vitro skin fluxes were 180, 177, and 14 micrograms/cm2/h for formulations A, B, and C, respectively. The systemic bioavailability of ketorolac acid from three transdermal formulations was evaluated in nine healthy subjects in a randomized three-way crossover fashion. Hill Top chambers were used as prototype dermal delivery devices to load the drug solution. This procedure was followed by the immediate application of devices to human subjects for 24 h. Blood samples were collected at various time intervals up to 48 h, and the samples were assayed by HPLC. The basic pharmacokinetic parameters were derived from the drug plasma concentration versus time plot. The maximum drug plasma concentrations were 1.265, 0.696, and 0.092 micrograms/mL for formulations A, B, and C, respectively. Formulation A provided the highest in vitro and in vivo transdermal delivery rate among the three formulations studied. An excellent correlation between the in vitro steady-state skin flux and the area under the curve of in vivo plasma drug concentration versus time was observed for all the three formulations.