Pharmacokinetic properties of 4‐fluoroamphetamine in serum and oral fluid after oral ingestion

Abstract

Introduction Each year, synthetic drugs occur in high numbers on the illicit drug market. But data on their pharmacology and toxicology are scarce. Therefore, a controlled study was performed to evaluate pharmacokinetic parameters of 4‐fluoroamphetamine (4‐FA) in humans and to compare it with effects. Methods Twelve subjects ingested 100 mg and five subjects also received 150 mg 4‐FA in a bitter lemon drink. Blood and oral fluid samples were taken during the following 12 hours and analyzed for 4‐FA and traces of amphetamine as impurity by liquid chromatography−tandem mass spectrometry (LC–MS/MS). Results For 12 hours after ingestion, the concentration‐time course of 4‐FA was similar to that of amphetamine with maximal concentrations appearing in serum after about 2 hours (in median 195 ng/mL after the 100 mg dose, range 155–316 ng/mL). The elimination half‐life was approximately 8–9 hours and shorter than that of amphetamine but it exhibited a marked variation (5.5–16.8 hours). In oral fluid, 4‐FA could also be detected for 12 hours and concentrations were higher than in serum. During the first 3 hours after ingestion concentrations were higher, most probably due to oral contamination. Serum concentrations in forensic cases were in the range of those observed in the present study suggesting dosages in recreational use in the range of those tested here. Conclusions The pharmacokinetic properties of 4‐FA are similar to that of amphetamine including a marked variation in elimination. However, recreational dosages may already exhibit prominent adverse effects and may even have life‐threatening consequences.

Analysis of 4‐fluoroamphetamine in cerumen after controlled oral application

“…In this study, cerumen of 12 subjects who had consumed the designer stimulant 4‐FA, which gained popularity especially in the Netherlands, 10 was analyzed. After the oral administration of 100 mg of 4‐FA to all subjects and 150 mg to five of them, not only cerumen but also blood and urine samples were collected during the 12 h study (results are given by de Sousa Fernandes Perna et al 6 and Toennes et al 11 ). Cerumen was sampled three times after the drug consumption: at baseline and after 1 h (both from the left ear) and after 12 h (from the right ear).…”

“…The concentrations in cerumen may, therefore, be proportional to that in the blood. The correlation of the drug amounts in cerumen was tested using the data from the corresponding serum samples (the 4‐FA data from the study described by Toennes et al 11 are given in Table 2). This includes serum concentrations at the time of the first cerumen sampling ( C 1 h ), the highest serum concentrations reached ( C max ), and the areas under the curve until 1 and 12 h (AUC 0 → 1 h , AUC 0 → 12 h ).…”

“…This is not surprising when compared with the study results obtained with another secretion product, saliva. The concentrations in the saliva were also unpredictable, exhibiting a wide variation of ratios with serum concentrations 11 …”