Identifying the route of administration
The rate at which a drug reaches its site of action is a critical factor governing the duration and the severity of the pharmacological response. If analytical findings are to be interpreted correctly, the route by which a drug is given should, therefore, always be considered. In a case of criminal poisoning it may be essential to establish the route of drug administration in order to corroborate evidence.
In some cases, simple facts give a clear indication of the route. Thus, residual drug in the stomach contents or gastrointestinal tract may point to oral ingestion, a needle mark in the arm suggests intravenous injection, and high concentrations in muscle tissue may point to intramuscular injection. However, in the majority of cases it is not reasonably possible to determine with any certainty the route of administration from toxicological data. When there is no direct evidence to indicate how the drug entered the body, drug: metabolite concentration ratios can be particularly helpful because rates and pathways of metabolism can vary markedly with the route of admin istration. Thus, drug: metabolite concentration ratios in the blood are high if a drug is given intravenously, because the drug is not subject to first-pass metabolism. A common example is diazepam. If this drug is given intravenously during emergency procedures, little if any nordiazepam is found in blood, whereas oral dosing always produces significant amount of metabolite. Concentration ratios can be low where the drug is given by mouth because of first-pass metabolism by the liver. Thus, more than 90% of orally administered fluphenazine is oxidised in the liver before it even reaches the systemic circulation.
The route-dependent variability of drug disposition into tissues may also provide useful information relating to the route of administration. Because of the physiological processes involved, substantially smaller amounts of an intra venously administered drug are partitioned into the liver than when the same drug is given orally. If death results rapidly following a large overdose by intravenous injection, the liver-to blood drug concentration ratio would therefore be lower than that observed had the drug been given by mouth. Thus, liver : blood ratios of 2.5 and 5.0 have been observed in pentobarbital fatalities involving intravenous and oral admin istration, respectively, and ratios of 1.3 and 4.2 have been found for intravenous and oral fatalities involving morphine.
