Hydroxyzine distribution in postmortem cases and potential for redistribution

McIntyre, Iain M.; Mallett, Phyllis; Trochta, Amber; Morhaime, Jacquelyn

doi:10.1016/j.forsciint.2013.04.013

Cited by 24 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A number of reports elaborating on, and supporting, this model have now been published (McIntyre & Mallett 2012;McIntyre & Meyer Escott 2012;McIntyre & Anderson 2012;McIntyre et al 2013a;McIntyre et al 2013b). Furthermore, a direct correlation between the postmortem peripheral blood and corresponding antemortem concentration -by consideration of the L/P ratio -has been expressed (McIntyre et al 2013c).…”

Section: Introductionmentioning

confidence: 99%

Identification of a postmortem redistribution factor (F) for forensic toxicology

McIntyre

2014

J Anal Sci Technol

View full text Add to dashboard Cite

Background: Postmortem redistribution (PMR) refers to the changes that may occur in drug concentrations after death. Consequently, postmortem concentrations in blood may not always replicate the antemortem drug levels. Literature supports the model describing drugs with a liver (L) concentration to peripheral blood (P) concentration ratio less than 5 (L/kg) being prone to little or no PMR. Conversely, drugs with a L/P ratio greater than 20 to 30 (L/ kg) have propensity for substantial PMR. Findings: Expanding upon this prior work, the current paper presents the concept of a postmortem redistribution factor (F) for a drug, which characterizes the direct relationship between postmortem peripheral blood and the corresponding antemortem whole blood concentration. Conclusions: Development of the concept of a "postmortem redistribution factor" will provide a more definitive and authoritative drug ranking, and possibly, numerical interpretation of PMR for forensic toxicologists.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of a postmortem redistribution factor (F) for forensic toxicology

McIntyre

2014

J Anal Sci Technol

View full text Add to dashboard Cite

show abstract

“…Thus, an elevated central blood level may somehow reflect the drug concentration in the heart. The central to peripheral blood concentration ratios have been investigated for various compounds [135][136][137][138] and their values are listed in the table in supplementary material. As drugs diffuse not only from the myocardium but also from other surrounding organs, these data in some cases may be misleading.…”

Section: Introductionmentioning

confidence: 99%

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Tylutki

Polak

2015

Biopharm & Drug Disp

View full text Add to dashboard Cite

ABSTRACT:Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart.

show abstract

“…Nevertheless, given recent information documenting the L/P ratio as a marker for PMR, these data support earlier impressions suggestive of potential for benztropine PMR. Based on criteria of L/P ratios exceeding 20–30 L/kg indicative of a propensity for significant PMR and ratios <5 L/kg indicating little to no propensity toward PMR , the L/P ratio in this case of 20.4 L/kg implies significant potential for PMR. On the other hand, based on the earlier C/P ratio model, these numbers suggest, arguably, only a minimal propensity for benztropine PMR, although the possibility of some degree of PMR occurring in the peripheral blood cannot be discounted.…”

Section: Resultsmentioning

confidence: 99%

Acute Benztropine Intoxication and Fatality

McIntyre

Mallett

Burton

et al. 2014

Journal of Forensic Sciences

Self Cite

View full text Add to dashboard Cite

A woman was found unresponsive with an empty bottle of Cogentin(®) prescribed to another. Admitted to an area hospital, her condition steadily declined until death 29 h after admission. Following toxicological screening on hospital (admission) whole blood, the only significant compound detected was benztropine. Benztropine was confirmed at 0.28 mg/L - the highest antemortem blood concentration recorded in a case of toxicity or fatality uniquely associated with benztropine. A second serum antemortem specimen showed a benztropine concentration of 0.19 mg/L. Despite over 24 h in the hospital, benztropine was also found in the postmortem specimens collected at autopsy. Peripheral blood, central blood, liver, and gastric concentrations were 0.47 mg/L, 0.36 mg/L, 9.6 mg/kg, and 44 mg, respectively. These results indicate that benztropine exhibited a potential difference between whole-blood and serum (plasma) concentrations. Additionally, in consideration of literature data, benztropine was found indicative of a compound prone to at least some postmortem redistribution.

show abstract

Hydroxyzine distribution in postmortem cases and potential for redistribution

Cited by 24 publications

References 24 publications

Identification of a postmortem redistribution factor (F) for forensic toxicology

Identification of a postmortem redistribution factor (F) for forensic toxicology

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Acute Benztropine Intoxication and Fatality

Contact Info

Product

Resources

About