Pharmacology of drugs in saliva
Opiates (heroin, 6-monoacetylmorphine, morphine, codeine and related opiates)
The major metabolite found in oral fluid after heroin use is 6-MAM (saliva: plasma ratio of 6; Cone1993; Jenkins et al. 1994, 1995; Moore et al. 2001). The heroin parent drug was found in oral fluid for up to 24 hours after heroin had been smoked and up to 60 minutes after heroin had been injected, with a S/P ratio after intravenous administration of 2.13, range 0.12–7.2 (Jenkins et al. 1995). If heroin is snorted (Cone 1993) or smoked (Jenkins et al. 1995), very high levels of heroin (in the mg/L range) may be detected in oral fluid for several hours after use because of deposition of the parent drug in the oral cavity. In addition to heroinand6-MAM, morphine may be found in saliva after heroin use. An average saliva: plasma ratio of 0.67 (range 0.1–1.82) for morphine in oral fluid after the intravenous administration of heroin was reported by Jenkins et al. (1995). Euphoria after heroin use occurs rapidly and diminishes within the first hour, which parallels the time course of heroin in saliva and blood. Miosis caused by heroin peaks approximately 15 minutes after administration by smoking or intravenous injection, and persists for up to 4 hours. Miosis parallels the time course of saliva and blood concentrations of 6-MAM and morphine (Jenkins et al. 1994). Morphine appears in saliva after the administration of morphine sulfate with a saliva: plasma ratio of 0.2 (Cone 1993). Hydromorphone is found in saliva, with the saliva: plasma ratio in the elimination phase ranging from 0.25 to 2.32 for eight subjects with both inter-individual and intra-individual variation (Ritschel et al. 1987). Hydromorphone was detected in saliva by radioimmunoassay for up to 10 hours after intravenous administration of 2–5 mg of hydromorphone.
Pholcodine is found in saliva in the range of 1.5–350 lg/L after oral doses of 20 and 60 mg (Chen et al. 1988). The saliva: plasma ratio was 3.6, calculated from the mean areas under the concentration–time curves for plasma and saliva. Pholcodine was detectable in saliva for 20 hours after the last dose on day 11 of chronic dosing. After administration of codeine, the drug is found in saliva with a saliva: plasma ratio of 3.3 (Cone 1993; Kim et al. 2002). O’Neal et al. (1999) reported a mean saliva: plasma ratio of 3.7-+0.28 when measured 2 to 12 hours after the oral administration of 30 mg of codeine and concluded that saliva codeine concentrations could be used to estimate plasma concentration via the saliva: plasma ratio. Codeine- 6-glucuronide was not found in saliva.
O’Neal et al. (2000) reported that codeine concentrations in saliva collected by expectoration or draining of unstimulated oral fluid were 1.3–2.0 times higher than codeine concentrations in oral fluid collected by swabbing with absorptive devices (OraSure, Salivette and Finger Collector containing AccuSorb foam). As expected from the Henderson–Hasselbalch equation above, codeine concentrations in unstimulated saliva collected by expectoration were 3.6 times higher than concentrations in specimens collected by expectoration after acidic stimulation by citric acid. Other prescription opiates and opioids reported in oral fluid include hydrocodone, oxycodone (Jones et al. 2002), dihydrocodeine (Skopp et al. 2001) and fentanyl (Silverstein et al. 1993).
Ingestion of 5.2–40 g of poppy seeds produced saliva opiate-positive results at 15 minutes, but not at 1 hour. However, no 6-MAM was found in saliva after ingestion of poppy seeds. Speckl et al. (1999) evaluated a collection device (ClinRep) that consisted of a treated cotton roll which was then centrifuged and the oral fluid collected and filtered before extraction and GC-MS analysis. They reported that the concordance of the analytic results for opiates of the saliva samples with urine was 93% for a cut off limit of 100 lg/L and 98% for a cut-off limit of 300 lg/L.
