E-DRUG: Norgestrel and combined contraceptive pills (contd)

[Kirsten Myhr <myhr@online.no>]

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E-DRUG: Norgestrel and combined contraceptive pills (contd)
-----------------------------------------------------------
I think other E-druggers have elaborated a lot on the issue of racemates 
vs. enantiomers and I'm no expert, but let me just add that in 1990-91 
this was a topic in many prominent journals. I would therefore like to 
give those of you that would like to know some more a few references. 
Norgestrel is not mentioned in any of the lists I've seen in the articles, 
the main "problem" drugs have been beta-blockers, other cardivascular 
drugs and steroids. 

Of interest, since thalidomide is now back in use: German researchers 
showed some 20 years ago that in mice, although the two stereoisomers were
sedative, only one was responsible for the teratogenicity. I wonder what's
the case with the effect in leprosy.

To make one point: I have a feeling it is probably easier to produce
racemates and most pre-registration clinical trials are therefore done on
the racemates. If it is discovered that the effect is caused by one
enantiomer, few would then like to spend a lot of money doing new trials
unless deemed necessary, e.g. when the racemate product is facing generic
competition (patent has expired).

The references:
Lennard MS. Clinical pharmacology thorugh the looking glass: reflections 
on the racemate vs enantiomer debate. Br J Clin Pharm 1991;31:623-5

Ariens EJ. Racemic therapeuthics - ethical and regulatory aspects. Eur J
Clin Pharmacol 1991;41:89-93

Tracy TS. Stereochemistry in pharmacotherapy: when mirror images are not
identical. Ann Pharmacother 1995;29:161-5

Ed. Chirality. Lancet 1990;336:1100-1

Lee EJD, Williams KM. Chirality. Clinical pharmacokinetic and
pharmacodynamic considerations. Clin Pharmacokinet 1990;18:339-45

Smith DF. The stereoselectivity of drug action. Pharmacol Toxicol 
1989;65:321-31

Pang YT. Stereoisomerism in drug molecules. Aust Prescr 1989;12:19-25

Some views from the Medical Product Agency on the documentation for chiral
drugs. News from the Swedish Medical Agency 1990;no 2:82-7

Ms Kirsten Myhr, MScPharm, MPH
Bygdoy Alle 58B
0265 Oslo
Norway
Tel: +47 22 56 05 85 (h)
Fax: +47 22 24 90 17 (w) Tel: +47 22 24 88 55 (w)
E-mail: myhr@online.no
or (w): kirsten.myhr@helsetilsynet.dep.telemax.no


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