**3.4.1 PK-PD model**

Methadone, among other opiate drugs, causes a decrease in the value of index, testosterone/creatinine in urine, in a dose-dependent manner. We can dose Methadone by increasing o decreasing the daily dosage to reach index values of 20-30 mg / g, the Clinical Surrogate Endpoint. (Lozano et al 2008b, 2009b).

Once the steady-state and a pharmacological response, ranging between the 20-80% of maximal effect, is reached we can estimate the optimal dose required to achieve its Clinical Surrogate Endpoint, using equation 2
