Party pills and drug-drug interactions.
OBJECTIVE
This study aimed to explore the potential for drug-drug interactions involving benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP). This was achieved by determining the effects of BZP and TFMPP on the metabolism of drugs commonly found in the clinical setting by using pooled human liver microsomes.


METHODS
Incubations consisted of a probe substrate (drug of interest), a potential inhibitor (BZP or TFMPP), a suitable enzyme co-factor (NADPH), and pooled human liver microsomes. Loss of substrate was determined by analysing pre- and post-incubation concentrations in the samples by using HPLC/UV analysis.


RESULTS
Both TFMPP and BZP were found to inhibit the metabolism of dextromethorphan, caffeine, and ethinyloestradiol. These are reported substrates of CYP2D6, CYP1A2, and CYP3A4 respectively. Greater enzyme inhibition was observed in TFMPP microsomal assays in comparison to those using BZP. The metabolism of omeprazole was not affected, suggesting that BZP and TFMPP do not have a significant inhibitory effect on CYP2C19.


CONCLUSIONS
The inhibitory effects of BZP and TFMPP observed in this study are of potential significance to clinical practice because CYP2D6, CYP1A2, and CYP3A4 are involved in the metabolism of many commonly used drugs. Knowledge about the observed inhibitory effects will be a useful aid in preventing toxicity when drugs metabolised by these isoenzymes are taken with party pills.
Murphy
Meghan
M
School of Pharmacy, University of Auckland, Auckland, New Zealand.
Antia
Ushtana
U
Chang
Hsin-Yao
HY
Han
Jae Young
JY
Ibrahim
Ushtana
U
Tingle
Malcolm
M
Russell
Bruce
B
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects*; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D011336:Probability; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity
D010879:Piperazines