Hydrocodone

Common/Brand Names
Hycodan, Vicoprofen, Lorcet, Lortab, Norco, Vicodin, Tussionex, Maxidone, Hysingla ER
Expected Screen Results
Opiates
Expected Confirmation Results
Hydrocodone / Norhydrocodone / Hydromorphone
Confirmation Cutoff
20
ng/mL
Detection Time
Up to
3
Days
Notes
Metabolized by CYP2D6 and CYP3A4. Some studies show that 10% of population can't metabolize hydrocodone to hydromorphone; positive hydrocodone and negative hydromorphone could be due to inter-individual metabolism or hydromorphone is below LOQ. Hydromorphone is a minor metabolite and will usually see a lower concentration in chronic users than PRN users.
drug image

INTRODUCTION

Hydrocodone is a Schedule II semi-synthetic opiate derived from codeine or thebaine and is part of the phenanthrenes group that is based off the morphine structure and is a µ receptor agonist 1-2. It is prescribed under the following trade names: Anexsia, Damason-P, Hycodan, Lorcet, Lortab, Maxidone, Norco, Panacet, Hysingla™ER, Tussionex, Vicodin, Vicoprofen, Zohydro ER and Zydone. Hydrocodone is prescribed as narcotic analgesic for moderate to moderately severe pain and as an antitussive agent.  

PHARMACOLOGY 

ADMINISTRATION:

Hydrocodone is administered orally in a syrup, tablet and capsule with typical doses of 2.5-10 mg. Additionally, hydrocodone can be prescribed in an extended release formulation up to 120 mg. Frequently, an over the counter analgesic such as acetaminophen or ibuprofen is also present in the medication. 

DISTRIBUTION:

Following a single 5 or 10 mg oral dose of hydrocodone, peak serum concentrations occurred around 1.5 hours with a half-life of 3.4-8.8 hours4.  Peak concentrations of hydrocodone and its metabolites in urine occurred between 3-9 hours5.

METABOLISM:

Hydrocodone is metabolized extensively by demethylation at the O and the N positions in order to form hydromorphone (HM) and norhydrocodone (NHC), respectively 4. HC is metabolized through the CYP2D6 enzyme to produce the pharmacologically active metabolite HM. Slow metabolizers of hydrocodone have a genetic polymorphism of CYP2D6 that reduces this metabolic pathway and adversely affects the therapeutic efficacy 6-7. Pharmacologically inactive NHC is metabolized by CYP3A4 and is unaffected by the CYP2D6 polymorphism. 

EXCRETION:

Renal excretion accounts for approximately 85% of the glucuronide metabolites and in the 72 hour urine, 12% is eliminated as the parent drug 1,8.  

METHODS OF ANALYSIS

The opiate screening methodology utilized for the detection of hydrocodone is the Enzyme Immunoassay (EIA) with an approximately equivalent cutoff concentration of 300 ng/mL 9. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) is used to confirm and quantify hydrocodone, with a cutoff concentration at 20 ng/mL. Subsequent to analyses, the urine concentrations of hydrocodone and its two primary metabolites are reported.

INTERPRETATION

For patients regularly prescribed hydrocodone, the parent drug along with the metabolites should be detected in the urine. In a study conducted by Heltsely, et al., of 5595 specimens analyzed for hydrocodone, 72.2% contained both hydrocodone and metabolites, 13.6% contained only metabolites of hydrocodone and 4.1% contained only parent drug 10. If only hydrocodone is present in high concentrations, the possibility of patient tampering should be considered.

The interpretation of patients prescribed hydrocodone should be conducted with caution since HM is also prescribed and/or abused. NHC is metabolized directly from hydrocodone and has a longer detection time; therefore it may assist with interpretation 11. Additionally, hydrocodone preparation may contain codeine as an impurity up to 0.15%. and hydrocodone is a known impurity in oxycodone preparations up to 1.0% and HM preparations up to 0.1% 12.

 

References
  1. Ropero-Miller. J.D., Goldberger.B.A (2001) Opioids. In Shaw.L.M. (eds). The Clinical Toxicology Laboratory Contemporary Practice of Poisoning Evaluation, Chapter 6. AACC Press. Washington, D.C., 73-95.
  2. Stout, P. R.  (2009) Opioids. In Ropero-Miller J. D., Goldberger B.A. (eds.) Handbook of Workplace Drug Testing 2nd edition, Chapter 10.  AACC Press. Washington, D.C., 289-316.
  3. U.S. Food and Drug Administration, (2013) Zohydro (3395199). Retrieved from FDA.gov http://www.accessdata.fda.gov/drugsatfdadocs/label/2013/202880s000lbl.pdf.
  4. Baselt, R. C. (2011) Disposition of Toxic Drugs and Chemicals in Man, 9th Edition. Biomedical Publications, Seal Beach, CA, 812-814.
  5. American Association of Medical Review Officers. (2013) New HSS Sponsored Study on Metabolism and Excretion Patterns of Hydrocodone in Urine Following Controlled Single-Dose Administration. MRO Alert8, 1-3.
  6. Cone, E.J., Darwin, C.W., Gorodetzky, C.W., Tan.T., (1978) Comparative Metabolism of Hydrocodone in man, Rat, Guinea Pig, Rabbit and Dog. Drug Metabolism and Disposition, 6, 448-493.
  7. Mikus. G., Weiss. J. (2005) Influence of CYP2D6 Genetics on Opioid Kinetic, Metabolism and Response. Current Pharmacogenomics3, 43-52.
  8. U.S. Food and Drug Administration, (2008). Vicoprofen CS-III. Retrieved from FDA.gov http://www.accessdata.fda.gov/drugsatfdadocs/label/2008/020716s010lbl.pdf.
  9. Emit II Plus Opiate Assay (2010) [Package Insert]. Newark, DE: Siemens Healthcare Diagnostics.
  10. Heltsley, R., Zichterman, A., Black, D.L., Cawthon, B., Robert, T., Moser,F., et al. (2010) Urine Drug Testing of Chronic Pain Patients. II. Prevalence Patters of Prescription Opiates and Metabolites. Journal of Analytical Toxicology, 34, 32-38.
  11. Valtier.S., Bebarta, V.S., (2012) Excretion Profile of Hydrocodone, Hydromorphone and Norhydrocodone in Urine Following Single Dose Administration of Hydrocodone to Healthy Volunteers. Journal of Analytical Toxicology, 36, 507-514.
  12. American Association of Medical Review Officers. (2010) Interpreting Test Results for Prescription Opiates. MRO Alert,3, 1-3.