Blood levels of pentobarbital sodium, meprobamate, and tybamate in relation to clinical effects

Experiments are reported in which single therapeutic doses of central depressant drugs were given to normal volunteers with simultaneous measurement of blood levels of drug and clinical effects. In the case of pentobarbital, only one of nine possible correlations was significant; after eight hours, high serum levels of pentobarbital were correlated with high aggressive scores on a mood scale. In the case of meprobamate, none of six possible correlations at two time periods was significant, although the relationship between sleepy scores and high plasma levels approached significance both times. This relationship was confirmed for meprobamate in a third study, in which the presence of sleepiness as a symptom was associated with significantly higher levels of drug than its absence. Similar findings applied to tybamate in regard to the symptom of drowsiness. The relatively poor correlation between blood levels of central depressant drugs and clinical symptoms may be related in part to the difficulty of measuring relevant effects in normal men. In larger part, however, it may be due to the fact that social and personal factors more strongly influence the appearance of clinical effects from mild central depressants than do serum levels of the drugs.