DCBA
06-09-2008, 08:20 AM
How long would it take for a urine drug screen to be negative after the ingestion of aspirin with 8 mg of codeine and caffeine (222)
Acording to this study:...
Specific Question: How long would it take for a urine drug screen to be negative after the ingestion of aspirin with 8 mg of codeine and caffeine (222)?
Type of Question: Long Answer
Type of Long Answer Question (please underscore): Pharmacy & Therapeutics Review/ Drug Review/ Newsletter/ Controversial Literature Evaluation
BACKGROUND
The brand name of a popular Canadian over-the-counter medication containing aspirin, caffeine, and 8 mg of codeine per tablet is 222. It is widely available throughout most of Canada. The use of codeine in the United States is more restrictive. It is a prescription medication in most states, although several states do permit non-prescription use when it is monitored by a licensed pharmacist. The popularity of mail order pharmacy and the proximity of the U.S.-Canadian border have led to the availability of 222’s and the unrestricted use of this medication in the U.S.
Random drug testing has become a widespread practice in workplaces throughout the U.S. There are many different ways to screen for illicit drugs, and usually the least invasive methods (e.g. testing urine, hair, or saliva) are preferred. Urine test kits have become commercially available and involve the use of an immunoassay that can detect many classes of drugs. Positive results are then sent for confirmation by gas chromatography-mass spectrometry (GC-MS).
Opiates are one class of drugs that are routinely screened for in urine drug tests. A common commercially available assay, the Emit II Plus Opiate Assay, detects codeine and it’s metabolites: morphine and morphine-3-glucuronide. It can also detect hydromorphone, meperidine, and nalorphine because they are structurally related to morphine.1
The Department of Health and Human Services has set the current cut-off for a positive result in urine at 2000 ng/ml of opiates in both the initial and confirmation stages of testing.2 Originally, the Department of Health and Human Services set the cut-off for a positive test result at 300 ng/ml of opiates in the initial and confirmation phases of screening.3 It was determined that these levels were much too stringent when a high level of false positives occurred, many of which could be attributed to the ingestion of food products containing opiates, such as poppy seeds.
DISCUSSION
Study #1
Lafolie P et al4 studied the pharmacokinetics of codeine based on plasma and urine concentrations after oral dosing. Thirteen test subjects were given either a 25 or 50 mg dose of codeine in a randomized and open trial. After a two-week washout period, subjects were given the alternate dose, and the urine and plasma analysis was repeated. Urine was screened for opiates with the EMIT assay set for a positive cut-off of 300 ng/ml, and further analyzed by GC-MS for total codeine, morphine, and norcodeine. The results were analyzed to determine the time it took to achieve the last positive in the EMIT assay. The 25 mg dose resulted in an average time of 29.7 hours (range= 19.8-38.6 h.) for opiate levels to fall below 300 ng/ml. The 50 mg dose resulted in an average time of 40.4 hours (range= 30.0-52.2 h.) for opiate levels to fall below 300 ng/ml.
When dosing recommendations are followed, 222’s are taken as two tablets (16 mg codeine total) every 4-6 hours. Using conservative estimates, it can be assumed that the time for opiate levels to fall below 300 ng/ml would be at least equal or somewhat less than an average of 29.7 hours. It is impossible to extrapolate the results to determine when the levels would have fallen below the less stringent cut-off of 2000 ng/ml to give a negative drug test.
Unfortunately, the small number of test subjects limited this study. In this small group, there was wide variability in the time it took for opiate levels to fall below the 300 ng/ml cut-off. The metabolism of codeine has been shown to be influenced by genetics, and some individuals can be classified as poor or rapid metabolizers. The ability to metabolize codeine and its metabolites would have a direct impact on the clearance of the opiates tested for in the assay. It would also affect how long levels would stay above the 300 ng/ml cut-off.
Study #2
Cone EJ et al5 studied the pharmacokinetics of codeine and morphine excretion in urine following the intra-muscular (IM) injection of 60 and 120 mg of codeine. Codeine and morphine levels were quantified by GC-MS. Four male subjects were injected with either codeine or placebo and urine was collected in 12-hour increments for up to 96 hours. If a wash out period between testing days occurred, it was not indicated. The authors’ pooled the data to achieve a mean time in which the last positive urine specimen was detected. When the cut-off was set at 2000 ng/ml of total codeine, levels fell below the cut-off at approximately 24 hours following an IM dose of 60 mg. Total morphine levels fell below 2000 ng/ml at approximately 16 hours.
Again, it was difficult to apply the results of this study to the drug information question at hand. This study was plagued by the same problems as the first: a small number of test subjects, and the possibility of genetic variation within the individuals being studied. It had the additional problem of only including male subjects, and the route of administration of the codeine (IM) was different. When the limited scope of this study was taken into account, if a 60 mg dose of codeine resulted in urine levels that were less than 2000 ng/ml at 24 hours, then a dose of 16 mg given orally would probably not be detected in urine at the same cut-off value at 24 hours.
CONCLUSION
It was difficult to draw a conclusion based on the studies that were available. The data from the first study suggested that an oral dose of codeine 25 mg would not be detected in urine after an average of 29.7 hours, with a cut-off of 300 ng/ml. The data from the second study suggested that an IM dose of codeine 60 mg would not be detectable in urine after 24 hours, with a cut-off of 2000 ng/ml. Extrapolation of this data to determine the time frame in which an oral dose of codeine 16 mg would no longer be detected in urine via a drug test would be tenuous at best.
You can find the study in here (just replace the xx with tt ..)
hxxp://home.rochester.rr.com/hilburger/codeinerevised.doc
So if you piss dirty for the OPI 2000 and MOP 300 tests, sorry doc, that can't be!!! the only thing i took this week besides my methadone was this 222 that i had around the house because i had a terrible headache last night/this morning.
;)
Acording to this study:...
Specific Question: How long would it take for a urine drug screen to be negative after the ingestion of aspirin with 8 mg of codeine and caffeine (222)?
Type of Question: Long Answer
Type of Long Answer Question (please underscore): Pharmacy & Therapeutics Review/ Drug Review/ Newsletter/ Controversial Literature Evaluation
BACKGROUND
The brand name of a popular Canadian over-the-counter medication containing aspirin, caffeine, and 8 mg of codeine per tablet is 222. It is widely available throughout most of Canada. The use of codeine in the United States is more restrictive. It is a prescription medication in most states, although several states do permit non-prescription use when it is monitored by a licensed pharmacist. The popularity of mail order pharmacy and the proximity of the U.S.-Canadian border have led to the availability of 222’s and the unrestricted use of this medication in the U.S.
Random drug testing has become a widespread practice in workplaces throughout the U.S. There are many different ways to screen for illicit drugs, and usually the least invasive methods (e.g. testing urine, hair, or saliva) are preferred. Urine test kits have become commercially available and involve the use of an immunoassay that can detect many classes of drugs. Positive results are then sent for confirmation by gas chromatography-mass spectrometry (GC-MS).
Opiates are one class of drugs that are routinely screened for in urine drug tests. A common commercially available assay, the Emit II Plus Opiate Assay, detects codeine and it’s metabolites: morphine and morphine-3-glucuronide. It can also detect hydromorphone, meperidine, and nalorphine because they are structurally related to morphine.1
The Department of Health and Human Services has set the current cut-off for a positive result in urine at 2000 ng/ml of opiates in both the initial and confirmation stages of testing.2 Originally, the Department of Health and Human Services set the cut-off for a positive test result at 300 ng/ml of opiates in the initial and confirmation phases of screening.3 It was determined that these levels were much too stringent when a high level of false positives occurred, many of which could be attributed to the ingestion of food products containing opiates, such as poppy seeds.
DISCUSSION
Study #1
Lafolie P et al4 studied the pharmacokinetics of codeine based on plasma and urine concentrations after oral dosing. Thirteen test subjects were given either a 25 or 50 mg dose of codeine in a randomized and open trial. After a two-week washout period, subjects were given the alternate dose, and the urine and plasma analysis was repeated. Urine was screened for opiates with the EMIT assay set for a positive cut-off of 300 ng/ml, and further analyzed by GC-MS for total codeine, morphine, and norcodeine. The results were analyzed to determine the time it took to achieve the last positive in the EMIT assay. The 25 mg dose resulted in an average time of 29.7 hours (range= 19.8-38.6 h.) for opiate levels to fall below 300 ng/ml. The 50 mg dose resulted in an average time of 40.4 hours (range= 30.0-52.2 h.) for opiate levels to fall below 300 ng/ml.
When dosing recommendations are followed, 222’s are taken as two tablets (16 mg codeine total) every 4-6 hours. Using conservative estimates, it can be assumed that the time for opiate levels to fall below 300 ng/ml would be at least equal or somewhat less than an average of 29.7 hours. It is impossible to extrapolate the results to determine when the levels would have fallen below the less stringent cut-off of 2000 ng/ml to give a negative drug test.
Unfortunately, the small number of test subjects limited this study. In this small group, there was wide variability in the time it took for opiate levels to fall below the 300 ng/ml cut-off. The metabolism of codeine has been shown to be influenced by genetics, and some individuals can be classified as poor or rapid metabolizers. The ability to metabolize codeine and its metabolites would have a direct impact on the clearance of the opiates tested for in the assay. It would also affect how long levels would stay above the 300 ng/ml cut-off.
Study #2
Cone EJ et al5 studied the pharmacokinetics of codeine and morphine excretion in urine following the intra-muscular (IM) injection of 60 and 120 mg of codeine. Codeine and morphine levels were quantified by GC-MS. Four male subjects were injected with either codeine or placebo and urine was collected in 12-hour increments for up to 96 hours. If a wash out period between testing days occurred, it was not indicated. The authors’ pooled the data to achieve a mean time in which the last positive urine specimen was detected. When the cut-off was set at 2000 ng/ml of total codeine, levels fell below the cut-off at approximately 24 hours following an IM dose of 60 mg. Total morphine levels fell below 2000 ng/ml at approximately 16 hours.
Again, it was difficult to apply the results of this study to the drug information question at hand. This study was plagued by the same problems as the first: a small number of test subjects, and the possibility of genetic variation within the individuals being studied. It had the additional problem of only including male subjects, and the route of administration of the codeine (IM) was different. When the limited scope of this study was taken into account, if a 60 mg dose of codeine resulted in urine levels that were less than 2000 ng/ml at 24 hours, then a dose of 16 mg given orally would probably not be detected in urine at the same cut-off value at 24 hours.
CONCLUSION
It was difficult to draw a conclusion based on the studies that were available. The data from the first study suggested that an oral dose of codeine 25 mg would not be detected in urine after an average of 29.7 hours, with a cut-off of 300 ng/ml. The data from the second study suggested that an IM dose of codeine 60 mg would not be detectable in urine after 24 hours, with a cut-off of 2000 ng/ml. Extrapolation of this data to determine the time frame in which an oral dose of codeine 16 mg would no longer be detected in urine via a drug test would be tenuous at best.
You can find the study in here (just replace the xx with tt ..)
hxxp://home.rochester.rr.com/hilburger/codeinerevised.doc
So if you piss dirty for the OPI 2000 and MOP 300 tests, sorry doc, that can't be!!! the only thing i took this week besides my methadone was this 222 that i had around the house because i had a terrible headache last night/this morning.
;)