SEPTEMBER 1998table of contentsNUMBER ONE
WHAT LIES AHEAD

P450 Metabolism
Managing Drug Interactions

Today, there are several updated p450 pharmacology charts on the Internet to help health providers assess potential drug interactions. The following chart tells you what p450 liver pathway is used by a given drug. If two drugs use the same pathway, they could affect one another. In general, a P450 substrate is any drug that uses the cytochrome p450 enzyme pathway. P450 inhibitors (INH) generally increase concentrations of other drugs. P450 inducers (IND) generally decrease concentrations of other drugs. P450 enzymes are classified using Roman numerals and letters. Almost half of all human drugs use p450 3A4; another 30 percent use p450 2D6.

On the Web
Regularly updated p450 drug-interaction sites include the American College of Clinical Pharmacology (www.accp.com/p450.html), Georgetown Medical Center (www.dml.georgetown.edu/depts/pharmacology/davetab.html), and San Francisco General Hospital (insite.ucsf.edu). There are also excellent practical guides for managing HIV drug interactions at the Health Care Communications Group website (www.healthcg.com/hiv/treatment/interactions), and Project Inform (www.projinf.org).

Tip: Discuss possible drug interactions with your doctor before taking any new drug. Read the package insert for a drug to find out if it's cytochrome p450 metabolized, or ask a pharmacist for help.

Updated as of June 20, 1998 (extrapolated from clinical pharmacology p450 tables: ACCP, Georgetown, Healthcare Communications Group, etc. See "When Drugs Fail").

NRTIs
Namep450 pathway/action
AZT, ddI, ddC, 3TC, d4T, abacavirMost of drug is excreted unchanged from kidneys in urine.
NNRTIs
Namep450 pathway/action
nevirapine Moderate p450 IND; 3A4 NH
delavirdine 3A4 INH, 2D6 INH
* DMP 266 (efavirenz, Sustiva)Moderate p450 IND; uses multiple pathways; has some inhibitory effect
NUCLEOTIDE DRUGS
Namep450 pathway/action
adefovir dipivoxil100 percent excreted from kidneys in urine
PROTEASE INHIBITORS
Namep450 pathway/action
saquinavir Weak 3A4 INH
ritonavir Strong 2D6 INH, 3A4 INH, moderate p450 inducer; also: INH 1A2, 2C9, 2C19, 2E1
indinavir 3A4 INH, 2D6 INH
nelfinavir Moderate 3A4 INH and moderate p450 inducer
* amprenavir (141W94)3A4 INH and substrate
CHOLESTEROL/TRIGLYCERIDE/LIPID LOWERING DRUGS
Namep450 pathway/action
ColestidNot p450 metabolized, but affects absorption of drugs in GI tract
QuestranNot p450 metabolized, but affects absorption of drugs in GI tract
Niacin Not liver metabolized; excreted in urine
HMC COA Reducatase Inhibitors All use p450 3A4; may interact with statins avoid in patients with liver disease
Troglitazone2C9 INH, 2C19 INH, 3A4 INH; an insulin sensitizer, stresses liver
Lopid (gemfibrozil)Partly liver metabolized
Atromid-S (clofibrate)Partly liver metabolized
Lorelco (probucol)Not p450 metabolized. Risk for individuals with arrythmia
DRUGS USED TO TREAT WASTING:
Namep450 pathway/action
serostim (growth hormone)Some liver metabolism, cleaved in kidneys
Testosterone ethanate 3A4, 3A5-7
17-ALKYLATED ANABOLIC STEROIDS
Namep450 pathway/action
Oxandrolone/Oxandrin, Likely 3A4; 60 percent of drug unchanged in urine excreted
Decadorobulin (nandrolone decanoate)Likely 3A4; increases serum estradiol
Methonolone steroid (primbolon depot) Likely 3A4; illegal in U.S.,imported, best for women
OTHER COMMONLY USED DRUGS
Namep450 pathway/action
hydroxyurea50 percent of drug excreted unchanged from kidneys in urine; the rest metabolized in liver
caffeine1A2, 3A4 IND
Ethinyl Estradiol1A2, 3A4, 3A5-7
oral contraceptives (general)3A4
Biaxin (clarithromycin) 3A4
acetaminophen1A2, 2E1
doxorubicin2D6, 3A4 substrate
(R) warfarin1A2, 2C19
(S) warfarin2C9, 2C19
cyclophosphamide2C19, 2B6, 3A4
ibuprofen2C9
CodeineD6 INH, minor 3A4
Calcium channel blockers3A4
Beta blockers2D6
Antidepressants: clomipramine, in part; desipramine, imipramineMostly 2D6
trimetrexate1A2
vincristine3A4, 3A5-7
gluccocorticoids3A4 IND (primarily a substrate)
p450 inhibitors
Namep450 pathway/action
grapefruit juice3A4 INH, (in gut wall), 1A2
TMP/SMX (Bactrim, Septra)2C9 INH
erythromycin1A2 INH, 3A4 INH
clarithromycin IA2, 3A4 INH
ketoconazole Strong 3A4, INH, 3A5-7, INH, 2C19, 1A2
itraconazole Strong 3A4 INH
flucanazole 2C9 INH, 3A4 INH
cimetidineStrong 1A2 INH, 3A4 INH, 2C
lovastatin2C9
vinblastine2D6, INH, 3A4, 3A5-7
p450 inducers
Namep450 pathway/action
Viagraweak inhibitor, p450 inducer
nicotine1A2 IND
progesterone2C19 IND, 3A4
rifabutinStrong 3A4 IND
rifampin Strong 3A4 IND, 1A2 IND, 2C9 IND, 2C19 IND, 3A5-7 IND
insulin1A2
prednisone2C19
dilantinModerate inducer, 3A4, 2D6, 1A2, 2C
tegretilModerate 3A4, 2D6, 2C
isoniazid2E1 IND, 2C

  September 1998

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  Last modified 8/27/98.
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