Figure 5.

A schematic representation of the entire PK–PD model of leuprolide on the plasma testosterone level after SC administration of (a) leuprolide solution and (b) SR depot. Solid lines with arrows indicate the elimination or distribution of PKs, or indicate the production or elimination of responses. Dashed lines with arrows indicate the stimulatory or inhibitory effect of PDs. N_R, the ratio of entrapped leuprolide in the non-capsuled section; D_R, the ratio of entrapped leuprolide in the diffusive section; E_R, ratio of entrapped leuprolide in the erosive section; k_a, the absorption rate constant; k_d, the diffusive-release constant; k_t, the erosive-release constant; CL, the total clearance; C_p, the plasma concentration of leuprolide; C_E, the concentration of leuprolide in the effect site; E_max, the maximum effective capacity; EC₅₀, the half maximal effective concentration; h, the Hill equation constant; k_in, the zero-order constant for production of response; k_out, the first-order rate constant for loss of response; k_f,on, the first-order constant for onset of inhibitory; k_f,off, the first-order constant for onset of inhibitory.