Gamma-hydroxybutyrate and ethanol effects and interactions in humans.
BACKGROUND
Gamma-hydroxybutyrate (GHB) is a common drug of abuse that can produce serious toxicity, particularly when used with other sedatives. We examined the individual and combined effects of GHB and ethanol in human volunteers.


METHODS
Sixteen healthy adults (7 men) were given 50 mg/kg GHB (Xyrem), 0.6 g/kg ethanol in 2 doses, alone and combined in a double-blind, placebo-controlled, crossover study. Plasma concentrations, heart rate (HR), blood pressure (BP), and oxygen saturation (O2sat) were serially monitored for 24 hours.


RESULTS
Adverse events included 2 instances of hypotension and 6 episodes of vomiting with GHB-plus-ethanol ingestion. Oxygen saturation was decreased by GHB and ethanol individually, and maximally decreased by the drugs combined (max -2.1% +/- 0.3%, P < 0.0001 vs placebo). Compared with baseline, systolic and diastolic BP were significantly decreased, and HR was increased by ethanol but not affected by GHB alone (maximum systolic BP change -15.7 +/- 3.0 mm Hg, P = 0.0006; maximum HR change 13.5 +/- 2.3 beats per minute, P = 0.006). Ethanol coingestion resulted in 16% higher GHB maximal plasma concentration and 29% longer elimination half-life, indicating possible enhanced bioavailability or reduced clearance of GHB caused by ethanol, however, these effects were not statistically significant.


CONCLUSIONS
Modest doses of GHB do not affect hemodynamic function, but O2sat was decreased. Gamma-hydroxybutyrate-plus-ethanol resulted in more adverse effects, including gastrointestinal disturbances, hypotension, and decreased O2sat, but only minimal pharmacokinetic interactions were observed.
Thai
Dung
D
Amgen Corporation, Thousand Oaks, CA, USA.
Dyer
Jo Ellen
JE
Benowitz
Neal L
NL
Haller
Christine A
CA
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D012016:Reference Values; D012881:Skin Temperature / Q000187:drug effects; D012978:Sodium Oxybate / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced
D002492:Central Nervous System Depressants; D000431:Ethanol; D012978:Sodium Oxybate; D010100:Oxygen