3 results for Antia, Ushtana

  • The metabolism and pharmacokinetics of BZP and TFMPP – ‘party pill’ drugs

    Antia, Ushtana (2009)

    Doctoral thesis
    The University of Auckland Library

    Benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) are recreational drugs and the major constituents of a number of 'party pills'. Previous studies of these drugs have indicated that they may be metabolised by hepatic enzymes of the cytochrome P450 (CYP) family. However, the metabolism, pharmacokinetic properties and drug interactions of these drugs are poorly understood. This thesis aimed to develop and apply an analytical method to the detection of these drugs, to investigate their in vitro and in vivo biotransformation, to describe their pharmacokinetic properties in humans and describe the potential for drug-drug interactions. An analytical method consisting of a reversed phase HPLC system coupled with MS using an Agilent Zorbax CI8 HPLC column (4.6 x 150 mm, 5 μm) with guard column (C18, 4.6 x 10 mm, 5 μm) at 20 °C and a mobile phase of ammonium formate buffer (pH 4.5, 0.01 M, solvent A) and acetonitrile (solvent B) with a phase gradient and total run time of 15 minutes was developed and validated for the detection of BZP and TFMPP plus three hydroxylated metabolites in plasma. In vitro inhibition assays with human liver preparations were used to study the metabolism of these drugs. By using inhibitors quinidine, furafylline and troleandomycin it was found that CYP2D6, CYP1A2 and CYP3A4 metabolise both BZP and TFMPP. CYP2D6 poor metaboliser status was shown to compromise metabolism of TFMPP both in vitro and in vivo. For the human pharmacokinetic study, three groups of seven healthy human participants were dosed with either BZP HCI (200 mg) or TFMPP HCl (60 mg) or both drugs (100 mg ofBZP HCl and 30 mg ofTFMPP HCl). BZP and TFMPP reached maximum plasma concentrations of 262 ng/mL and 24.1 ng/mL at 75 minutes and 90 minutes respectively, and were cleared from the plasma of participants within 24 hr. In vitro and in vivo interactions were evident in this data, most notably the in vivo inhibition of the hydroxylation of each drug in the presence of the other. In summary, this thesis presents the results of some of the first studies on the metabolism and pharmacokinetics of these drugs in humans and sets the stage for future studies on the pharmacology of these commonly-used recreational drugs.

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  • Pharmacokinetics of `party pill' drug N-benzylpiperazine (BZP) in healthy human participants.

    Antia, Ushtana; Lee, Hee; Kydd, Robert; Tingle, Malcolm; Russell, Bruce (2009)

    Journal article
    The University of Auckland Library

    There have been many reports of benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) being used as recreational drugs which have been widely marketed in the form of [`]party pills' since the late 1990's. However, there is no information currently available describing the pharmacokinetics of these drugs in humans. Human plasma concentrations of BZP were measured in blood and urine samples taken from healthy adults (n = 7) over 24 h following a 200 mg oral dose of BZP. Plasma concentrations of BZP were found to peak at 262 ng/mL (Cmax) and 75 min (Tmax). Plasma concentrations of the major metabolites of BZP, 4-OH BZP and 3-OH BZP, were found to peak at 7 ng/mL (at 60 min) and 13 ng/mL (at 75 min) respectively. The elimination half-life (t1/2) for BZP was found to be 5.5 h. Clearance (Cl/F) was found to be 99 L/h. The results of this study indicate that BZP may be detectable in plasma for up to 30 h following an oral dose. Additionally, several urinary metabolites can be detected

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  • Metabolic interactions with piperazine-based 'party pill' drugs

    Antia, Ushtana; Tingle, Malcolm; Russell, Bruce (2009-07)

    Journal article
    The University of Auckland Library

    Objectives Tarty pills' have found use worldwide its a substitute for amphetamine-derived designer drugs. Whilst some information exists about the metabolism of these drugs, there is little information about their ability to inhibit the metabolism of co-administered drugs. This study aimed to determine whether predictions call be made about. A interactions between 'party pills' Constituents and other drugs metabolised by the same cytochrome P450 (CYP) isoenzymes.Methods The inhibitory effects of seven benzyl and phenyl piperazines were measured in microsomal incubation assays of probe substrates for five major CYP isoenzymes. In addition, the metabolism of benzylpiperazine and trifluromethylphenylpiperazine, the two Most commonly used Constituents Of 'party pills' was investigated using human liver microsomes assays and known inhibitors of CYP isoenzymes.Key findings All piperazine analogues tested showed significant inhibitory activity against most, if not all, isoenzymes tested. The metabolism of benzylpiperazine (BZP) and trifluromethylphenylpiperazine (TFMPP) involved CYP2D6. CYP1A2 and CYP3A4. Furthermore, BZP and TFMPP inhibited each other's metabolism.Conclusions Fluorophenylpiperazine, methoxyphenylpiperazine, chlorophenylpiperazine, methylbenzylpiperazine and methylenedioxybenzylpiperazine had significant inhibitory effects on CYP2D6, CYP1A2, CYP3A4, CYP2C19 and CYP2C9 isoenzymes but each piperazine had a different inhibitory profile. The metabolic interaction between BZP and TFMPP may have clinical implications, as these agents are often combined in 'party pills'.

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