PHARMACOKINETICS OF DEXAMETHASONE AND ITS RELATIONSHIP TO DEXAMETHASONE SUPPRESSION TEST OUTCOME IN DEPRESSED-PATIENTS AND HEALTHY CONTROL SUBJECTS

The pharmacokinetics of dexamethasone (DEX) were studied in 9 drug-fre e melancholically depressed patients and 10 healthy control subjects m atched by sex and age, Each subject received 1 mg of DEX administered orally and by the (IV) route at 11:00 PM and serial blood samples were collected over the next 17 hours until 4:00 PM, There were no signifi cant differences between the diagnostic groups and DEX bioavailability , peak plasma level, time to maximum concentration, or in elimination half-life after oral administration. Bioavailability estimates indicat ed that DEX absorption was incomplete and variable (mean = 61%, SD = 1 4) in controls as well as depressed patients. In both groups there was a wide interindividual variability in plasma DEX levels following bot h oral and IV routes of administration. This variability could not be reliably predicted by differences in age, sex, or weight between subje cts, The factors that accounted for most of the variability in 4:00 PM plasma DEX levels after oral administration were clearance, bioavaila bility, and time to reach maximum concentration. Plasma DEX levels wer e lower in 3 depressed nonsuppressors compared to 3 matched controls w ho suppressed. No single pharmacokinetic factor was shown to be respon sible for the lower DEX levels in the depressed nonsuppressors, These results indicate that plasma DEX levels need to be measured in each in dividual during the DST procedure so that this information may be take n into consideration when interpreting DST results, (C) 1997 Society o f Biological Psychiatry.