Alpha(1)-acid glycoprotein (AAG) and serum protein binding of methadone inheroin addicts with abstinence syndrome

Objective: To quantify serum protein levels and protein-binding of methadon e in vitro in heroin-addicted patients showing objective signs of heroin ab stinence. Subjects and methods: Serum samples were obtained from patients ( n = 27) hospitalized to participate in a methadone detoxification program a nd from healthy volunteers (n = 21). The severity of the abstinence syndrom e was assessed before blood sampling using a standardized scale. Concentrat ions of both albumin and alpha(1)-acid glycoprotein (AAG) were measured in all serum samples. The protein-binding of alpha(1)-methadone was determined by the ultrafiltration technique and the unbound concentration was measure d by liquid scintillation counting. Results: The mean of the AAG concentrat ions was significantly increased in patients showing signs of withdrawal wh ile the albumin concentrations did not change. Also, the unbound methadone was significantly decreased in this group when compared to the control. A p ositive correlation (Pearson r = 0.48; p < 0.005) indicates that AAG levels rise during abstinence as the score of withdrawal symptoms increases. Addi tionally, pooled data from all individuals show the binding of methadone to be related to AAG (r = 0.46. p < 0.05) levels and not to albumin. Conclusi ons: The observed changes in protein-binding in abstinence individuals sugg est the need for increased dosages of methadone when such patients are trea ted. Levels of AAG or protein-binding appear to be components of the interi ndividual variance observed in the response to methadone treatment, hence t hese variables could be included in future kinetic and dynamic studies.