Antiretroviral and Dietary Supplement Drug Interaction Studies

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Robert DiCenzo, Pharm.D.

Department of Pharmacy Practice
School of Pharmacy and Pharmaceutical Sciences
University at Buffalo
E-mail: robert_dicenzo@urmc.rochester.edu

Siberian ginseng at generally recommended doses did not inhibit drug metabolism through CYP2D6 or CYP3A4 isoforms.

Donovan et al conducted a study with 12 subjects to evaluate the effect of Siberian ginseng (SG) on dextromethorphan (DM) and alprazolam (ALPZ) metabolism which are probes for CYP2D6 and CYP3A4 isozymes, respectively. At baseline, each subject received 30mg of dextromethorphan (DM) and alprazolam (ALPZ) 2 mg orally with 30 to 60ml of water. Urine samples were obtained immediately after drug administration for 8 hours as baseline measurement for CYP2D6 activity through the ratio of DM to its metabolite. ALPZ pharmacokinetics were estimated by obtaining blood prior to drug administration, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours. After a minimum of a 7 day wash-out period, subjects took standardized Siberian ginseng (SG) 485mg capsules for 14 days. Siberian ginseng was administered as one capsule twice daily (8am and 8pm). At day 15, subjects returned to clinic, were given 30mg of DM, 2 mg of ALPZ, and SG 485mg capsule twice daily and urine and blood samples were drawn identically to baseline. Compared to baseline, there was no significant difference between the ratio of dextromethorphan and its metabolite after administration of SG (n=12; p>0.05). Compared to baseline, none of the ALPZ pharmacokinetic parameters measured was different after SG administration. (n=12; p>0.05). ALPZ given alone was bioequivalent to ALPZ given with SG (AUC0-¥ geometric mean ratio (95% CI) of 1.01 (0.96-1.06). In conclusion, Siberian ginseng did not significantly affect the metabolism of either the CYP2D6 or CYP3A4 probe; therefore, SG would not be expected to alter the metabolism of medications that are metabolized by either of these pathways.