EFFECT OF LIPOPHILIC VEHICLES ON IN-VIVO SKIN PENETRATION OF METHYL NICOTINATE IN DIFFERENT RACES

Studies on racial differences in percutaneous penetration have mainly focused on measurements of either the pharmacodynamic response of a dr ug or skin reactivity to irritants. In order to clarify the contributi on of the barrier stratum corneum to the overall drug penetration rate in different races, an in vivo permeability study was conducted with methyl nicotinate as the model drug. Four races (Caucasians, Hispanics , Blacks, Asians) were investigated. The drug was dissolved in various lipophilic vehicles (dimethicone 100, light mineral oil, isopropyl my ristate, medium chain triglycerides) at concentrations that provide eq ual drug escaping tendencies. Drug solutions were applied to the upper arms of 48 subjects (four races with 12 subjects each) with a glass c hamber system. To avoid drug depletion, drug disappearance rates were measured under steady-state conditions by the so-called difference met hod. Drug flux among the four races increases in the following order: Blacks < Asians < Caucasians < Hispanics. The effect of race almost re aches significance level (P = 0.067). Fisher's PLSD post-hoc procedure indicated a significant difference between drug penetration in Hispan ics and Blacks (P = 0.009) suggesting structural or functional differe nces in the stratum corneum. Enhancement factors were calculated from the steady-state flux values, (i.e. drug disappearance rates per area unit) for each face. Significant enhancing effects (P = 0.0001) were o bserved with the vehicles isopropyl myristate and mineral oil with all races.