Pharmacogenomics meets Pharmacokinetics
You have been asked to make an initial dosage recommendation for a 111.6 kg patient. The drug to be administered is extensively metabolized with an fe value close to zero and an F value of 0.22 when given orally. The single metabolic pathway is enzymatically catalyzed by CYP2D6 which has a number of genetically controlled alleles. There are at least extensive (EM) and poor (PM) metabolizers and there are reports of intermediate alleles as well. The average apparent volume of distribution is 0.46 L/Kg. The distribution of kel values in the population has been studied and found to be bi-modal as shown in the figure below. The patient has been genetically tested and found to a slow metabolizer of this drug. Using this information calculate a twice daily oral dose of this drug to maintain an average concentration of 1 mg/L.
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