Semi-Synthetic, Highly Prolific NAME THAT
DRUG SUBMITTED BY QUEST DIAGNOSTICS, INC. T
his semi-synthetic drug was first synthesized in 1916, and placed into clinical use in Germany in
1917. In the 1920s, patients reported hav- ing euphoric effects when using this com- pound. It was first introduced to the U.S. market in 1939. Te original goal of this new analgesic was to replace other drugs that carried a higher risk for developing dependence. Tis drug may be clinically administered through a variety of routes: intravenously, intramuscularly, intra-na- sally, subcutaneously, rectally, epidurally, and orally. It was used in northern Europe mainly for the treatment of acute pain. Other countries, such as Canada, Austra- lia and the United States have also used it as a combination drug for the treatment of moderate pain. Tis drug is currently available in both “immediate release” and “controlled release” formulations. Following an oral administration of the
immediate release form of the drug, peak plasma concentrations are observed at one hour post-dose, with a half-life of three hours. Te oral bioavailability of the drug averages 60-87 percent, with an onset of ac- tion beginning at 10-15 minutes post-dose. Te pain-relieving effect lasts approxi- mately four to six hours. Te compound is distributed to skeletal muscle, liver, intes- tinal tract, lungs, spleen and brain tissues. Te drug is broken down to numerous metabolites and both the parent com- pound and the metabolites are primarily excreted in the urine and sweat. Its primary metabolite is pharmacologically active and is also available as a prescription drug. Renally-impaired patients may exhibit drug and/or metabolite accumulation. Hepatic metabolism of the compound is medi- ated by Cytochrome P450 enzymes (CYP 3A4 and CYP 2D6). Approximately 5-10 percent of Caucasian patients are deficient
42 datia focus
in CYP 2D6, and are thus considered to be “poor metabolizers” of the drug. Conse- quently, not only certain disease states, but genetic differences may also contribute to the effectiveness and toxicity of this drug. Although the drug was originally
introduced to replace other addictive pain medications, the present compound may also be highly addictive. Individuals who abuse the drug do so primarily to experi- ence a sense of euphoria. Persons who habitually use the drug may develop a tolerance, requiring higher doses to obtain the desired effect. Adverse side effects may include headaches, constipation, nausea, dizziness, dry mouth, drowsiness, loss of appetite, fainting and a slowed heartbeat. Overdose side effects may include muscle weakness, confusion, pinpoint pupils and possible death. Laboratory testing for this drug is a well-
established technology and available in most commercial and hospital laboratories. Tere is also increasing interest in the mea- surement of this drug in oral fluid and hair testing. Testing for this drug is oſten per- formed using an immunoassay technique. For a more sensitive screening, a specific immunoassay, rather than an assay for its pharmacological class, should be utilized. Currently, there are no FDA-cleared im- munoassays for screening this drug in oral fluid. When required, gas chromatography/ mass spectrometry (e.g. GC/MS[/MS]) or liquid chromatography/mass spectrometry (LC/MS[/MS]) is used for confirmation. In 1963, California declared abuse of
this drug as the source of one-third of all drug addictions in the state. In 1970 the compound was classified as a Schedule II drug under the federal Controlled Substances Act. In 1996, a pharmaceuti- cal manufacturer introduced a timed- release version of this drug. Within two
years, the new product accounted for 80 percent of the company’s profits. In 2010, the manufacturer reformulated the product to include an abuse-resistant polymer to decrease the abuse potential. In 1998, it was estimated that 11.5 tons of this drug was manufactured. That number increased to over 75 tons in 2007. In 2007, the United States was es- timated to have consumed 82 percent of the world’s supply of this drug. This drug is not the most commonly prescribed member of its class—ranking 23rd
on the
list of the most commonly prescribed drugs in 2011—but it may receive the most media mentions. Between 2006 and 2011, the prescription dispensing of this product increased by 43 percent. The 2010 Monitoring the Future survey indicates that 2.1 percent of 8th 4.6 percent of 10th cent of 12th
graders, graders and 5.1 per- graders misused one of the
pharmaceutical preparations of this drug in the past year. Today the compound is cited as one of the country’s most abused prescription drugs and, according to the DEA, the most frequently encountered prescription drug by law enforcement in 2009. At an estimated “street price” of $1 per mg, it is now considered to be more expensive than heroin. While the Department of Transporta-
tion (DOT) rules do not currently in- clude testing for this drug, if the Medical Review Officer (MRO) was to learn of its use, a “safety concern letter” would typi- cally be sent to the employer. In January of 2012, the Substance Abuse and Mental Health Services Administration (SAM- HSA) administrator accepted its Drug Testing Advisory Board’s unanimous recommendation to consider adding prescription Schedule II drugs to the federal drug testing program. At the same
fall 2013
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