Revisited: Therapeutic and toxic blood concentrations of more than 1100 drugs and other xenobiotics

Abstract

In order to assess the significance of drug/substance levels measured in intensive care medicine and clinical and forensic toxicology as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. We revisited and expanded our 2012 compilation of therapeutic and toxic plasma concentration ranges as well as half-lives of now more than 1100 drugs and other xenobiotics. Data have been abstracted from original papers, text books, and previous compilations and have been completed with data collected in our own forensic and clinical toxicology laboratories. We compiled the data presented in the table and the corresponding annotations over the past 30+ years. A previous compilation was completely doublechecked, revised, and updated, if necessary. In addition, more than 200 substances, especially drugs who have been introduced since 2012 to the market as well as illegal drugs and other xenobiotics which became known to cause intoxications were added. We carefully referenced all data. Moreover, the annotations providing details were updated and revised, when necessary. For more than 1100 drugs and other xenobiotics, therapeutic ("normal") and, if data was available, toxic, and comatose-fatal plasma/blood concentrations as well as elimination half-lives were compiled in a table. In case of intoxications, the blood concentration of the substance and/or metabolite better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications as well as to support forensic and clinical expert opinions.

Mitochondrial Permeability Transition Pore Sealing Agents and Antioxidants Protect Oxidative Stress and Mitochondrial Dysfunction Induced by Naproxen, Diclofenac and Celecoxib

“…For example, the absorption of the compound may be minimal, the processes of distribution, metabolism and elimination may lead to higher or lower concentrations in target organs than could be expected from an even distribution of the compound in the body [24]. Therefore, in this study we used plasma concentrations for tested drugs in therapeutic and toxic range for more realistic estimate of human exposure [25][26][27].…”

Inhibitory effects of sulfonylureas and non‐steroidal anti‐inflammatory drugs on in vitro metabolism of canagliflozin in human liver microsomes

“…In the present in vitro study, niflumic acid, a potent UGT1A9 inhibitor, was used as a positive control and produced substantial inhibition of M7 metabolite formation at concentrations below therapeutic plasma levels. The in vitro IC 50 for niflumic acid was 1.86 ± 0.03 μ m , compared with typical plasma concentrations in the range of 2–35 μg/ml (7–124 μ m ) (Schulz & Schmoldt, ). Based on these findings, we proceeded further and determined the K i value for niflumic acid against the M7 metabolite of canagliflozin, and characterized the mechanism of inhibition.…”

Severe poisoning with naproxen causing coagulopathy

“…The concentrations measured were therapeutic for acebutolol and its acylated metabolite (lower than 2 mg/L) and were supratherapeutic for citalopram (higher than 0.2 mg/L, therapeutic range between 0.05 and 0.11 mg/L) . Oxazepam and zopiclone concentrations were at toxic levels (>2 mg/L and >0.15 mg/L, respectively, whereas therapeutic ranges between 0.2 and 0.15 mg/L and 0.01 and 0.05 mg/L, respectively).…”

“…Oxazepam and zopiclone concentrations were at toxic levels (>2 mg/L and >0.15 mg/L, respectively, whereas therapeutic ranges between 0.2 and 0.15 mg/L and 0.01 and 0.05 mg/L, respectively). Naproxen concentration was higher than 200 mg/L (therapeutic range being between 20 and 100 mg/L) . Zopiclone and oxazepam contributed to the onset of a coma.…”