Abstract

The interpretation of postmortem cocaine concentrations is made in an attempt to estimate drug concentrations present at the time of death and thus infer not only drug presence but drug toxicity. Previous data suggest that changes in postmortem blood cocaine concentrations over time are not predictable and interpretation of cocaine levels should be done with caution. However, these data come from autopsy case series where vital information, such as blood cocaine concentration at the time of death, dose and time since last use, and postmortem interval is often not known. The purpose of this study was to characterize postmortem changes in cocaine and metabolite concentrations relative to premortem concentrations over time at two anatomic sites: peripheral blood and vitreous humor, in a controlled, large animal model. Juvenile swine were given cocaine HCl 10 mg/kg as an IV bolus which resulted in seizures and wide complex tachycardia. Five minutes after cocaine administration, animals were euthanized. At time of death and eight hours postmortem, femoral venous blood and vitreous humor (VH) samples were obtained for quantitation of cocaine, benzoyl ecgonine (BE), and ecgonine methyl ester (EME) by GC/MS. There were no significant increases over time in mean femoral vein concentrations of cocaine or BE. However, a large interanimal variability in direction and magnitude of concentration changes was seen. Mean EME concentrations at the femoral site increased significantly over 8 hours (P < 0.03). Mean VH cocaine concentrations at time of death were significantly lower than corresponding blood concentrations (P < 0.02). However, 8 hour postmortem VH cocaine concentrations increased in all animals and were similar to the femoral blood concentrations at time of death. These results emphasize the variability in postmortem cocaine concentrations and the need to consider the site of collection and postmortem interval as variables in interpreting postmortem cocaine and metabolite concentrations relative to premortem values.

References

1.
Hearn
W. L.
,
Keran
E. E.
,
Wei
,
H.
, and
Hime
,
G.
, “
Site-Dependent Postmortem Changes in Blood Cocaine Concentrations
,”
Journal of Forensic Sciences
 0022-1198, Vol.
36
, No.
3
,
05
1991
, pp.
673
-
684
.
2.
Shepherd
,
M. F.
,
Lake
,
K. D.
, and
Kamps
,
M. A.
, “
Postmortem Changes and Pharmacokinetics: Review of the Literature and Case Report
,”
The Annals of Pharmacotherapy
, Vol.
26
, No.
4
,
04
1992
, pp.
510
-
514
.
3.
Pounder
,
D. J.
and
Jones
,
G. R.
, “
Post-Mortem Drug Redistribution—A Toxicological Nightmare
,”
Forensic Science International
 0379-0738, Vol
45
, No.
3
,
04
1990
, pp.
253
-
263
.
4.
Vorpahl
,
T. E.
and
Coe
,
J. I.
, “
Correlation of Antemortem and Postmortem Digoxin Levels
,”
Journal of Forensic Sciences
 0022-1198, Vol.
23
, No.
2
,
04
1978
, pp.
329
-
334
.
5.
Sedman
,
A. J.
,
Wilkinson
,
P. K.
, and
Wagner
,
J. G.
, “
Concentrations of Ethanol in Two Segments of the Vascular System
,”
Journal of Forensic Sciences
 0022-1198, Vol.
21
, No.
2
,
04
1976
, pp.
315
-
322
.
6.
Prouty
,
R. W.
and
Anderson
,
W. H.
, “
The Forensic Implications of Site and Temporal Influences on Postmortem Blood-Drug Concentrations
,”
Journal of Forensic Sciences
 0022-1198, Vol.
36
, No.
2
,
03
1990
, pp.
243
-
270
.
7.
Jones
,
G. R.
and
Pounder
,
D. J.
, “
Site Dependence of Drug Concentrations in Postmortem Blood — A Case Study
,”
Journal of Analytical Toxicology
 0146-4760, Vol.
11
, No.
5
, Sept./Oct. 1987, pp.
186
-
190
.
8.
Briglia
,
E. J.
,
Bidanset
,
J. H.
, and
Cortivo
,
L. A.
, “
The Distribution of Ethanol in Postmortem Blood Specimens
,”
Journal of Forensic Sciences
 0022-1198, Vol.
37
, No.
4
,
07
1992
, pp.
991
-
998
.
9.
Marraccini
,
J. V.
,
Carroll
,
T.
,
Grant
,
S.
,
Halleran
,
S.
, and
Benz
,
J. A.
, “
Differences Between Multisite Postmortem Ethanol Concentrations as Related to Agonal Events
,”
Journal of Forensic Sciences
 0022-1198, Vol.
25
, No.
6
,
11
1990
, pp.
1360
-
1366
.
10.
Plueckhahn
,
V. D.
and
Ballard
,
B.
, “
Diffusion of Stomach Alcohol and Heart Blood Concentration at Autopsy
,”
Journal of Forensic Sciences
 0022-1198, Vol.
12
, No.
4
,
10
1967
, pp.
463
-
470
.
11.
Prouty
,
R. W.
and
Anderson
,
W. H.
, “
A Comparison of Postmortem Heart and Blood and Femoral Ethyl Alcohol Concentrations
,”
Journal of Analytical Toxicology
 0146-4760, Vol.
11
, Sept./Oct. 1987, pp.
191
-
197
.
12.
Jones
,
G. R.
, “
Postmortem Changes in Drug Levels: A Common Phenomenon?
,” presented at the
International Association of Forensic Toxicologists 23rd European International Meeting, sponsored by the National Ministry of Education, the Flanders Government, State University of Ghent, and National Science Foundation
,
Belgium
, August 24–27, 1986.
13.
Watson
,
W. A.
,
Godley
,
P. J.
,
Garriot
,
J. C.
,
Christopher Bradberry
,
J.
, and
Puckett
,
J. D.
, “
Blood Pentobarbital Concentrations During Thiopental Therapy
,”
Drug Intelligence and Clinical Pharmacy
 0012-6578, Vol.
20
, No.
4
,
04
1986
, pp.
283
-
287
.
14.
Koran
,
G.
and
MacLeod
,
S. M.
, “
Postmortem Redistribution Digoxin in Rats
,”
Journal of Forensic Sciences
 0022-1198, Vol.
30
, No.
1
,
01
1985
, pp.
92
-
96
.
15.
Curry
,
A. S.
and
Sunshine
,
I.
, “
The Liver: Blood Ratio in Cases of Barbiturate Poisoning
,”
Toxicology and Applied Pharmacology
 0041-008X, Vol.
2
,
1960
, pp.
602
-
606
.
16.
Baselt
,
R. C.
and
Cravey
,
R. H.
,
Cocaine, in Disposition of Toxic Drugs and Chemicals in Man
,
Year Book Medical Publishers, Inc.
,
Chicago, IL
,
1989
, pp.
208
-
213
.
17.
Dean
,
R. A.
,
Christian
,
C. D.
,
Sample
,
R. H. B.
, and
Bosron
,
W. F.
, “
Human Liver Cocaine Esterases: Ethanol-Mediated Formation of Ethylcocaine
,”
FASEB J
, Vol.
5
,
09
1991
, pp.
2735
-
2739
.
18.
Liu
,
Y.
,
Budd
,
R. D.
, and
Griesemer
,
E. C.
, “
Study of the Stability of Cocaine and Benzoylecgonine, Its Major Metabolite, in Blood Samples
,”
Journal of Chromatography
 0021-9673, Vol.
248
,
1982
, pp.
300
-
302
.
19.
Isenschmid
,
D. S.
,
Levine
,
B. S.
, and
Caplan
,
Y. H.
, “
A Comprehensive Study of the Stability of Cocaine and Its Metabolites
,”
Journal of Analytical Toxicology
 0146-4760, Vol.
13
, September/October 1989, pp.
250
-
256
.
20.
Baselt
,
R. C.
, “
Stability of Cocaine in Biologic Fluids
,”
Journal of Chromatography
 0021-9673, Vol.
268
, No.
3
,
10
1983
, pp.
302
-
305
.
21.
Matsubara
,
K.
,
Kagawa
,
M.
, and
Fukui
,
Y.
, “
In vivo and In vitro Studies on Cocaine Metabolism: Ecgonine Methyl Ester As a Major Metabolite of Cocaine
,”
Forensic Science International
 0379-0738, Vol.
26
, No.
3
.
11
1984
, pp.
169
-
180
.
22.
Beno
,
J. M.
and
Kriewall
,
S.
, “
Post Mortem Elevation of Cocaine Levels in Vitreous Humor
,” presented at the
1989 meeting of the Society of Forensic Toxicologists
,
Chicago, IL
, 18–21 Oct. 1989.
23.
McKinney
,
P.
,
Barta
,
D.
, and
Brent
,
J.
, “
Lidocaine Pretreatment and Cocaine-Associated Arrhythmias and Seizures in Swine
,”
Veterinary and Human Toxicology
 0145-6296, (abs) Vol.
35
, No.
4
,
08
1993
, p. 350.
24.
McKinney
,
P.
,
Barta
,
D.
, and
Brent
,
J.
, “
Treatment of Cocaine-Induced Arrhythmias and Seizures in a Porcine Model
,”
Veterinary and Human Toxicology
 0145-6296, (abs) Vol.
35
, No.
4
,
08
1993
, p. 350.
25.
McKinney
,
P.
,
Watson
,
W.
,
McIntyre
,
M.
,
Phillips
,
S.
,
Gomez
,
H. F.
, and
Brent
,
J.
, “
Time Related Postmortem Changes in Cocaine and Metabolites in Blood, Urine and Vitreous Humor
,”
Veterinary and Human Toxicology
 0145-6296, (abs) Vol.
34
, No.
4
,
08
1992
, p. 348.
26.
Michael
, et al
,
Journal of Clinical and Laboratory Medicine
,
1949
, Vol.
34
, pp.
1564
-
1568
.
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