title: Site-to-site variability of drug concentrations in skeletal muscle.
abstract: The homogeneity of drug concentrations in skeletal muscle was assessed in eight fatal overdoses. Ten to 30 random samples were taken from leg muscle weighing 1,650 to 7,985 g. For cases involving paracetamol the mean muscle-to-blood ratio ranged from 0.1 to 1.1 (n = 4) for amitriptyline 1.1 to 3.6 (n = 3), and for dothiepin 0.8 to 2.1 (n = 2). The coefficient of variance was large for all drugs, ranging from 10.5 (carbamazepine) to 50 (thioridazine). Skeletal muscle is not homogeneous with respect to drug concentrations in fatal overdose cases. Of 16 instances of drug detection in blood 2 (nortriptyline and promethazine) were not detected in muscle. Muscle-to-blood drug ratios varied significantly among cases, possibly influenced by survival time after drug ingestion. Quantitative interpretations of muscle drug levels present significant difficulties. However, skeletal muscle can be used for qualitative corroboration of blood analyses and is a suitable specimen for drug detection where none other is available.
authors.affiliation: Department of Forensic Medicine, University of Dundee, Scotland.
authors.forename: K R
authors.initials: KR
authors.lastname: Williams
authors.forename: D J
authors.initials: DJ
authors.lastname: Pounder
mesh_terms: D000082:Acetaminophen / Q000032:analysis / Q000493:pharmacokinetics / Q000506:poisoning; D002491:Central Nervous System Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000506:poisoning; D003986:Dibenzocycloheptenes / Q000032:analysis / Q000493:pharmacokinetics / Q000506:poisoning; D004308:Dothiepin / Q000032:analysis / Q000493:pharmacokinetics / Q000506:poisoning; D062787:Drug Overdose / Q000209:etiology / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007866:Leg; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D011398:Promethazine / Q000032:analysis / Q000493:pharmacokinetics / Q000506:poisoning; D015203:Reproducibility of Results; D013693:Temazepam / Q000032:analysis / Q000493:pharmacokinetics / Q000506:poisoning; D014018:Tissue Distribution
chemical_list: D002491:Central Nervous System Agents; D003986:Dibenzocycloheptenes; D000082:Acetaminophen; D013693:Temazepam; D011398:Promethazine; D004308:Dothiepin