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June 19, 1991, Vol 265, No. 23 >
ARTICLE | June 19, 1991

Clinical Pharmacology FREE

Marcus M. Reidenberg, MD
JAMA. 1991;265(23):3107-3109. doi:10.1001/jama.1991.03460230057008
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References

The two principal themes of clinical pharmacology, individualization of drug therapy and the scientific assessment of drugs in humans, continue to be integrated into the mainstream of medicine itself.

The major development that is helping to individualize therapy is the continuing advance of pharmacogenetics and its application to clinical problems. The discovery that some people were very slow metabolizers of debrisoquin (a drug used to test a pathway of drug metabolism), because they lack the gene for the normal enzyme, has led to new interest in understanding the genetic basis of individual variation in drug response. Many drugs, including some tricyclic antidepressants (eg, desipramine, imipramine, nortriptyline, and amitriptyline) and propafenone, are metabolized by this pathway.1 About 7% of the population is markedly deficient in this enzyme. Prescribing these tricyclic antidepressants for patients who have this enzyme deficiency can lead to high levels of the drugs and toxic effects at

REFERENCES

1 +
Brosen K.  Recent developments in hepatic drug oxidation . Clin Pharmacokinet. 1990;;18:220-239.
2 +
Lee JT, Kroemer HK, Silberstein DJ, et al.  The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone . N Engl J Med. 1990;;322:1764-1768.
3 +
Mortimer 0, Persson MS, Ladona MG, et al.  Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: relationship to the presence of immunoidentified cytochrome P-450IIDl . Clin Pharmacol Ther. 1990;;47:27-35.
4 +
Sindrup SH, Brosen K, Bjerring P, et al.  Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine . Clin Pharmacol Ther. 1990;;48:686-693.
5 +
Gonzales FJ, Skoda RC, Kimura S, et al.  Characterization of the common genetic defect in humans deficient in debrisoquine metabolism . Nature . 1988;;331:442-446.
6 +
Heim M, Meyer UA.  Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification . Lancet . 1990;;336:529-532.
7 +
Lennard L, Van Loon JA, Weinshilboum RM.  Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism . Clin Pharmacol Ther. 1989;;46:149-154.
8 +
The CAST Investigators.  Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction . N Engl J Med. 1989;;321:406-412.
9 +
Woosley RL.  CAST: implications for drug development . Clin Pharmacol Ther. 1990;;47:553-556.
10 +
Slutsker L, Hoesly FC, Miller L, et al.  Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer . JAMA . 1990;;264:213-217.
11 +
Mayeno AN, Lin F, Foote CS, et al.  Characterization of 'Peak E,' a novel amino acid associated with eosinophilia-myalgia syndrome . Science . 1990;;250:1707-1708.
12 +
Verpooten GA, Giuliano RA, Verbist L, Eestermans G, De Broe ME.  Once-daily dosing decreases renal accumulation of gentamicin and netilmicin . Clin Pharmacol Ther. 1989;:45:22-27.
13 +
Craig WA, Vogelman B.  The postantibiotic effect . Ann Intern Med. 1987;;106:900-902.
14 +
Naranjo CA, Sullivan JT, Kadlec KE, Woodley-Remus DV, Kennedy G, Sellers EM.  Differential effects of viqualine on alcohol intake and other consummatory behaviors . Clin Pharmacol Ther. 1989;;46:301-309.
15 +
Naranjo CA, Kadlec KE, Sanhueza P, Woodley-Remus D, Sellers EM.  Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers . Clin Pharmacol Ther. 1990;;47:490-498.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Brosen K.  Recent developments in hepatic drug oxidation . Clin Pharmacokinet. 1990;;18:220-239.
2 +
Lee JT, Kroemer HK, Silberstein DJ, et al.  The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone . N Engl J Med. 1990;;322:1764-1768.
3 +
Mortimer 0, Persson MS, Ladona MG, et al.  Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: relationship to the presence of immunoidentified cytochrome P-450IIDl . Clin Pharmacol Ther. 1990;;47:27-35.
4 +
Sindrup SH, Brosen K, Bjerring P, et al.  Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine . Clin Pharmacol Ther. 1990;;48:686-693.
5 +
Gonzales FJ, Skoda RC, Kimura S, et al.  Characterization of the common genetic defect in humans deficient in debrisoquine metabolism . Nature . 1988;;331:442-446.
6 +
Heim M, Meyer UA.  Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification . Lancet . 1990;;336:529-532.
7 +
Lennard L, Van Loon JA, Weinshilboum RM.  Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism . Clin Pharmacol Ther. 1989;;46:149-154.
8 +
The CAST Investigators.  Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction . N Engl J Med. 1989;;321:406-412.
9 +
Woosley RL.  CAST: implications for drug development . Clin Pharmacol Ther. 1990;;47:553-556.
10 +
Slutsker L, Hoesly FC, Miller L, et al.  Eosinophilia-myalgia syndrome associated with exposure to tryptophan from a single manufacturer . JAMA . 1990;;264:213-217.
11 +
Mayeno AN, Lin F, Foote CS, et al.  Characterization of 'Peak E,' a novel amino acid associated with eosinophilia-myalgia syndrome . Science . 1990;;250:1707-1708.
12 +
Verpooten GA, Giuliano RA, Verbist L, Eestermans G, De Broe ME.  Once-daily dosing decreases renal accumulation of gentamicin and netilmicin . Clin Pharmacol Ther. 1989;:45:22-27.
13 +
Craig WA, Vogelman B.  The postantibiotic effect . Ann Intern Med. 1987;;106:900-902.
14 +
Naranjo CA, Sullivan JT, Kadlec KE, Woodley-Remus DV, Kennedy G, Sellers EM.  Differential effects of viqualine on alcohol intake and other consummatory behaviors . Clin Pharmacol Ther. 1989;;46:301-309.
15 +
Naranjo CA, Kadlec KE, Sanhueza P, Woodley-Remus D, Sellers EM.  Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers . Clin Pharmacol Ther. 1990;;47:490-498.

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