Numerous surveys and clinical reports have suggested that Asians require a significantly smaller psychotropic dosage than others for comparable clinical effects. However, the existence of such an ethnic difference, as well as its causes, have not been objectively explored. In this study we propose to give small standard oral and parenteral tests doses of haloperidol to matched samples of immigrant Asian, Asian-American and Caucasian volunteer subjects, then measure plasma prolactin and haloperidol (free and total) levels, and the degree of micrographia in handwriting (as an index of extrapyramidal side effects). After adjusting for weight and body fat distribution, higher prolactin levels and incidence of micrographia in Asians would strengthen the hypothesis of an ethnic difference in dosage requirement. Whether this is caused by pharmacokinetic or receptor factors will be determined by whether the free haloperidol plasma levels are also elevated in Asians. The possible influence of culturally determined differences in gastrointestinal absorption and protein-binding will be examined by comparing levels after parenteral vs oral routes, and free vs total levels. The long-term accumulative effect of environmental pollutants on the pharmacokinetics will be examined through comparison of the two Asian groups with divergent life history.
NIH ExPorter
NIH ExPorter