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The following message was posted to: PharmPK
Dear group
We are planning a series of studies to explore in vivo drug-drug
interactions between Traditional African Medicines and antituberculosis
and antiretroviral medications. Our preferred probes are: midazolam
(CYP3A4), bupropion (CYP2B6), metoprolol (CYP2D6) and digoxin (P-gp).
We have not combined P-gp and CYP2D6 probes previously. Our IRB has
expressed concern regarding the potential additive depressant effect on
both AV nodal conduction and heart rate even though we exclude healthy
volunteers with clinically relevant ECG abnormalities and, orthostatic
hypotension and a heart rate below 50 beats per minute.
Unfortunately, metoprolol is the only viable CYP2D6 probe in South
Africa and only the 100mg SR tablets are available. Our hospital
pharmacists prepare a metoprolol solution for clinical use, so we are
able to reduce the dose.
Does any member of the group have any suggestions or experience using
single doses of metoprolol and digoxin in healthy volunteers?
Jan-Stefan
Dr J-S van der Walt
Division of Clinical Pharmacology
University of Cape Town
K45 Old Main Building
Groote Schuur Hostpital
Observatory 7925 Cape Town
South Africa
Tel:+27 21 406-6512
Fax:+27 21 448-0886
Email: js.vanderwalt.-at-.uct.ac.za
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The following message was posted to: PharmPK
Dear Dr.Walt,
If available you can try dextromethorphan for 3A, 2D6, and pgp. Check
the following reference by Di Marco MP "The effect of grapefruit juice
and seville orange juice on the pharmacokinetics of dextromethorphan:
the role of gut CYP3A and P-glycoprotein" in Life Sci. 2002 Jul
26;71(10):1149-60
We have used dextromethorphan in one of our cocktail studies.
Regards
Prasad
--
Siva Rama Prasad Kambhampati, PhD
Section Head, Clinical Evaluation of Specialty Products
MDS Pharma Services
621 Rose Street
Lincoln, NE-68502 USA
Email: Prasad.Kambhampati.aaa.mdsinc.com
Tel: 402-437-1130
Fax: 402-476-7598
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