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Elimination half-life of alpha-pyrrolidinovalerophenone in an acute non-fatal intoxication

Alpha-pyrrolidinovalerophenone (a-PVP, a-pyrrolidinopentiophenone or flakka) is a synthetic stimulant drug that belongs to the cathinone family.[1] We present a non-fatal a-PVP intoxication with drug quantification and a pharmacokinetic profile. A 19-year-old male was admitted to the hospital after presumed consumption of alcohol and drugs. During transport 15 mg of intravenous midazolam was administered to control agitation and tachycardia (174 bpm). On admission, the patient was agitated with persecutory delusions, bruxism, mydriasis, blood pressure (BP) 135/63 mmHg, and heart rate (HR) 157 bpm. The ECG revealed sinus tachycardia without signs of sodium channel blockade. Another 15 mg of midazolam, repeated doses of intravenous diazepam (total dose 175 mg during 33 h) and physical restraints were required. At eight hours post-admission (BP: 155/85 mmHg; HR: 137 bpm), the temperature reached 38 C and was controlled with physical cooling and paracetamol (1 g). At 32 h psychotic symptoms ceased and he admitted ethanol and ecstasy consumption (administration route, dose, and time at consumption were unknown). At 40 h, vital signs were normalized and he was discharged at 57 h post-admission. The poisoning severity score was 2 (moderate). Laboratory results on admission revealed leukocytosis (15.300/lL) and elevation of serum creatine kinase (1759 U/L) and myoglobin (611 ng/mL). Toxicological analyses involved: serum ethanol, that was undetectable (<0.10 g/L) by an enzymatic method (Abbott Diagnostics; Abbott Laboratories, Irving, TX), urine drug screening by immunoassay (DRIR , Abbott Diagnostics; Abbott Laboratories, Irving, TX) for amfetamine, ecstasy, cannabinoids, cocaine metabolite and opiates, that was also negative, and urine drug screen by gas chromatography coupled to mass spectrometry (Agilent 5975/6890R ; Agilent Technologies, Barcelona, Spain), that was positive for a-PVP and its metabolite a-(200-oxo-pyrrolidino)valerophenone. The following drugs were specifically ruled out: methylone, mephedrone, 3,4methylenedioxypyrovalerone (MDPV), para-methoxymethamfetamine, ketamine, and methoxetamine. At admission, a-PVP serum and urine levels were 23 ng/mL and 4451 ng/mg related to creatinine (mg), respectively. Eight serum samples were obtained between 4 and 42 h post-admission to describe a-PVP pharmacokinetic profile using non-compartmental methods. a-PVP peak concentration was 39 ng/mL, measured at 12 h post-admission. The terminal elimination half-life (t1/2) was 4.29 h, calculated using the formula t1=2 1⁄4 ln 2=k, where the elimination rate constant (k) was obtained from the slope of the terminal portion of the semi-logarithmic serum concentration vs. time curve (Figure 1). The area under the curve was 570.72 ng h/mL from 4 to 42 h post-admission. Data available on a-PVP serum concentrations in non-fatal cases are limited.[1,2] Serial concentrations and t1/2 have not been previously reported. The estimated a-PVP t1/2 is comparable to those published for close related drugs such as cathinone [3] (4.33 ± 1.7 h) and synthetic derivatives as MDPV [4] (1.88 h). These values are lower than those reported for classical drugs [5] as metilendioxymethamfetamine (8–9 h), methoxymethamfetamine (10–12 h), or amfetamine (12–15 h), suggesting a faster elimination for cathinones. Our study has limitations which should be considered. The estimated pharmacokinetic parameters are based on one patient and the toxicological screening cannot exclude all drugs. In conclusion, the calculated t1/2 might represent a first guidance to estimate the duration of symptoms, however further cases are essential to reinforce these data.