Pharmacogenomics

[Deleted member 43589]

I used testosterone undeconate injectable for many years. I injected 750mg every 12 weeks. People thought i was nuts when I told them I had a serum level of 921 at the end of a 12 week cycle. How could this be? When I was a competitive world class powerlifter I also only used 250mg of testosterone enanthate and was one of the tops' in the world in two different weight classes. More recently my doctor prescribed me 200mg of testosterone cypionate every 10 days and I again tested and had a 2103 serum level. I was kind of shocked to say the least. But could it be that some of us genetically metabolize drugs quite differently that others.

Pharmacogenomics is a relatively new field of study which is a combination of pharmacology and genomics. Technically, Pharmacogenomics analyzes how the genetic makeup of an individual affects their response to drugs. It deals with the influence of acquired and inherited genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with pharmacokinetics (drug absorption, distribution, metabolism, and elimination) and pharmacodynamics (effects mediated through a drug's biological targets). So Pharmacogenomics aims to develop rational means to optimize drug therapy, with respect to the patients' genotype, to ensure maximum efficiency with minimal adverse effects.

I know this type of study is done at the Cleveland Clinic or PGx testing typically involves taking either a small blood sample or a saliva sample. Specifically, the DNA in the sample will be extracted and examined with a process known as DNA sequencing. Very exciting field of study and I hope to have this done sometime in the future. Could explain why a few of us get very good results with very little amounts of drugs.

Here is a place here in Houston that does this testing

Laboratory Testing & Clinical Diagnostic Center in Houston TX | Tesis Labs Texas

Tesis Labs Texas is a state of the art laboratory testing and clinical diagnostic center in Houston TX. We focus on bridging the gap between the patient and the provider. Click the link to learn more about our testing services.

tesistexas.com

 

[Cataceous]

Metabolism of testosterone is perhaps simpler than that of many other drugs, though no doubt genes still have some influence via the relative amounts of the necessary enzymes in the liver. Wikipedia describes it this way:

Both testosterone and 5α-DHT are metabolized mainly in the liver. Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively. An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order. Androsterone and etiocholanolone are then glucuronidated and to a lesser extent sulfated similarly to testosterone. The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile. Only a small fraction (2%) of testosterone is excreted unchanged in the urine.​

[R]

The basic model for steady-state is:

Production_Rate(free testosterone) = Clearance_Rate(free testosterone) = MCR * Concentration(free testosterone)

The metabolic rate constant MCR represents the total action of the various enzymes that metabolize testosterone. The law of mass action explains the linear relationship. In any case, someone like you has a relatively lower value for MCR. Thus for a given production rate of testosterone—or total dose given over time—you must have a higher concentration of testosterone than someone with a higher MCR getting testosterone at the same rate.