Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CODEINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

Distribution of codeine, morphine, and 6-acetylmorphine in vitreous humor.

Two hundred and twenty-three vitreous humor specimens, which were obtained from a medical examiner's office, were found to be opiate positive (cutoff, 50 ng/mL) by fluorescence polarization immunoassay. All samples were analyzed for their free codeine, morphine, and 6-acetylmorphine contents by a gas chromatography-mass spectrometry protocol. 6-Acetylmorphine was found (cutoff, 10 ng/mL) in 41 specimens in the concentration range of 10-125 ng/mL. Twenty specimens had a free codeine-free morphine concentration ratio > or = 1. Eighty-five samples that were found to contain 50 ng/mL free morphine were further analyzed for their total codeine and total morphine contents. Total codeine-total morphine concentration ratios in 8 (of the 85 samples) were > or = 1, whereas this ratio in the others (only those with a codeine concentration high than 15 ng/mL were included) was significantly lower than 1. The codeine-morphine concentration ratio in vitreous humor appears to resemble that reported for blood and urine and can be used as the basis for differentiating between codeine- and morphine- (heroin-) induced fatalities.

Cause of Death↗
PubMedDate not supplied

Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum.

This study examined the disposition of cocaine, codeine, and metabolites in stratum corneum, sebum, and plasma collected from five African-American males after administrations of cocaine and codeine during a 10-week inpatient clinical study. The subjects were experienced, healthy drug users with a recent history of cocaine and heroin abuse. The first drug administration was delayed by three weeks to allow for the elimination of previously administered drugs from the body. Subjects received three 75 mg cocaine hydrochloride/70 kg doses by the subcutaneous route and three 60 mg codeine sulfate/70 kg doses by the oral route on alternating days beginning in week 4. The same dosing sequence was repeated in week 8 with doubled (x 2) doses. Pharmacological measures (heart rate, pupil diameter, subject "High" and "Liking") were obtained simultaneously with blood. Stratum corneum was collected by scraping regions of the back once each week. Sebum was collected periodically from the forehead by applying Sebutape patches for 1-2-h intervals. Plasma, stratum corneum, and sebum were analyzed for cocaine, codeine, and metabolites by gas chromatography-mass spectrometry. Peak plasma cocaine concentrations occurred within the 30 min following dosing and followed peak pharmacological effects. Peak plasma codeine concentrations occurred within 1-2 h of dosing and before peak pharmacological effects. Cocaine and codeine were the primary analytes in sebum and stratum corneum. After dosing, these drugs appeared in sebum within 1-2 h and were detected for 1-2 days. Peak-drug concentrations in stratum corneum occurred one day after completion of dosing; elimination of the drugs continued over the next 1-2 weeks after dosing. Overall, no definitive relationship was observed between drug concentrations in sebum and stratum corneum compared with dose. Interpretation of drug distribution and elimination in sebum and stratum corneum was complicated by possible contamination of specimens with drugs from sweat. The mechanism(s) for deposition of cocaine and codeine in sebum and stratum corneum appeared to be complex and could involve the transfer of drugs between different body fluids (i.e., sebum and sweat) and other matrices (i.e., skin and hair).

Administration, Oral↗
PubMed2003

Sensitivity, specificity, and efficiency in detecting opiates in oral fluid with the Cozart Opiate Microplate EIA and GC-MS following controlled codeine administration.

Oral fluid specimens (N = 1406) were collected from 19 subjects prior to and up to 72 h following controlled administration of oral codeine. Volunteers provided informed consent to participate in this National Institute on Drug Abuse Institutional Review Board-approved protocol. A modification of Cozart Microplate Opiate EIA Oral Fluid Kit (Opiate ELISA), employing codeine calibrators, was used for semiquantitative analysis of opiates, followed by gas chromatography-mass spectrometry (GC-MS) for the confirmation and quantitation of codeine, norcodeine, morphine, and normorphine in oral fluid. GC-MS limits of detection and quantitation were 2.5 microg/L for all analytes. The Substance Abuse and Mental Health Services Administration (SAMHSA) has proposed a 40-microg/L opiate screening and a 40-microg/L morphine or codeine confirmation cutoff for the detection of opiate use. Oral fluid opiate screening and confirmation cutoffs of 30 micro g/L are in use in the U.K. Utilizing 2.5-, 20-, 30-, and 40-microg/L GC-MS cutoffs, 26%, 20%, 19%, and 18% of the oral fluid specimens were positive for codeine or one of its metabolites. Six Opiate ELISA/confirmation cutoff criteria (2.5/2.5, 10/2.5, 20/20, 30/20, 30/30, and 40/40 microg/L) were evaluated. Calculations for Opiate ELISA sensitivity, specificity, and efficiency were determined from the number of true-positive, true-negative, false-positive, and false-negative results at each screening/confirmation cutoff. Sensitivity, specificity, and efficiency for the lowest cutoff were 91.5%, 88.6%, and 89.3%. Application of the cutoff currently used in the U.K. yielded sensitivity, specificity, and efficiency results of 79.7%, 99.0%, and 95.4% and similar results of 76.7%, 99.1%, and 95.1% when applying the SAMHSA criteria. These data indicate that the Opiate ELISA efficiently detects oral codeine use. In addition, the data, collected following controlled oral codeine administration, may aid in the interpretation of opiate oral fluid test results and in the selection of appropriate oral fluid screening and confirmation cutoffs.

Administration, Oral↗
PubMed1997

Urinary excretion of codeine, ethylmorphine, and their metabolites: relation to the CYP2D6 activity.

The formation of morphine from codeine and ethylmorphine is mainly mediated by the polymorphic enzyme CYP2D6. The objective of this study was to investigate whether CYP2D6 poor metabolizers (PM) and CYP2D6 extensive metabolizers (EM) would respond differently during testing for opiate drugs of abuse in urine after intake of these drugs. Five PM and five EM of dextromethorphan were administered single oral doses of codeine (25 mg) and ethylmorphine (25 mg), and the urinary excretion of parent compounds and selected metabolites was observed for 72 hours. Analysis was performed with GC-MS after hydrolysis of the glucuronide conjugates. Selected urine samples were screened for the presence of opiates by the Abbott ADx immunoassay method. The results from one PM and one EM were excluded because of technical analytical problems. EM excreted significantly more morphine than PM after intake of both codeine (6.5% vs. 1.1% of the dose; p < 0.05) and ethylmorphine (11.0% vs. 3.0% of the dose; p < 0.05). Screening results were positive significantly longer for EM than for PM after codeine intake (mean, 33 hours vs. 17 hours; p < 0.05), and the same trend, albeit nonsignificantly, was noted for ethylmorphine (mean, 33 hours vs. 24 hours). Regardless of CYP2D6 phenotype, significantly more morphine was formed after intake of ethylmorphine than after intake of codeine (7.0% vs. 3.8% of the dose; p < 0.05). There were high correlations between dextromethorphan metabolic ratios and the ratios of codeine to morphine, ethylmorphine to morphine, norcodeine to normorphine, and norethylmorphine to normorphine (r = 0.80 to 0.92; p = 0.030 to 0.001). Although this study should be interpreted with caution because of the few subjects included and the single-dose design, it demonstrates that the CYP2D6 phenotype clearly affects the results when testing for opiates in urine after intake of codeine and ethylmorphine.

Adult↗
PubMed1992

Infants and young children metabolise codeine to morphine. A study after single and repeated rectal administration.

1. Codeine was administered rectally to thirteen infants and young children undergoing elective surgery. Nine infants (6-10 months old) received a 4 mg suppository and four children (3-4 years old) an 8 mg suppository. Codeine and its metabolite morphine were measured in plasma by GC/MS. 2. The mean concentrations of codeine at 3, 4 and 5 h after administration were 240, 163 and 123 nmol l-1 in the younger and 309, 251 and 169 nmol l-1 in the older patients. The corresponding concentrations of morphine were 8.3, 7.4 and 4.5 nmol l-1 and 6.8, 5.5 and 2.8 nmol l-1 respectively. One patient in each age group had no detectable amounts of morphine. 3. In the four children, the rectal dose was repeated 6-hourly for four doses. The plasma concentrations of codeine and morphine following the fifth dose were similar to those after the first dose. The mean AUC(0,5 h) of morphine was 1.6% that of codeine. 4. In the infants the mean plasma half-lives of codeine and morphine were 2.6 and 2.5 h. The two infants with the lowest body weights had the longest half-lives. 5. The mean morphine/codeine concentration ratio was 4.3% in the infants and 1.6% in the children, suggesting impaired glucuronidation of morphine in the former group. The hourly concentration ratios were almost identical following the first and fifth dose in the children. 6. We conclude that at the age of 6 months infants are capable of O-demethylating codeine to morphine.

Biotransformation↗
PubMed1978

Effect of codeine phosphate, Lomotil, and Isogel on iileostomy function.

The effect on ileostomy function of codeine phosphate, Lomotil, or Isogel was tested in 20 subjects at home living a normal life, studied over two three-day periods on and off treatment. Codeine phosphate 60 mg three times daily was associated with a reduction in the mean total weight of ileostomy output and the ileostomy outputs of water, sodium, and potassium (p < 0.05). The proportion of faecal solids increased on codeine and the effluent appeared thicker but the output of faecal solids remained unchanged. Mean faecal fat increased on codeine. The transit rate from mouth to stoma was slower in four of the five subjects on codeine and a further two subjects withdrew from the trial with temporary intestinal obstruction while on the drug. Lomotil two tablets three times daily was associated with a small and statistically not quite significant fall in the mean total weight of ileostomy output and the ileostomy output of water. Sodium and potassium outputs in the effluent fell on Lomotil (p < 0.05) but the other parameters remained unchanged. Isogel 15 ml three times daily was associated with an increase in the mean total weight of ileostomy output and the ileostomy outputs of water, sodium, potassium, and faecal solids (p < 0.01). Although the effluent looked more viscid on Isogel, the proportion of faecal solids was unchanged. These results suggest that codeine phosphate has a beneficial effect on ileostomy function, reducing the loss of water and electrolytes, while Lomotil has a similar but less effective action in the dosage tested. By contrast, Isogel increases the ileostomy loss of water and electrolytes and will aggravate their depletion in patients with excessive fluid effluents. The increase in faecal fat associated with taking codeine phosphate suggests that it should be stopped before collecting specimens for faecal fat estimations.

Adolescent↗
PubMedDate not supplied

Comparison of the effects of acupuncture and codeine on postoperative dental pain.

The analgesic effects of acupuncture were compared with those of codeine in the treatment of postoperative dental pain in 40 healthy male volunteers 18 to 30 years old. Upon the patient's recovery from local anesthesia (lidocaine), he was asked by a trained observer to classify the intensity of his pain as none, mild, moderate, or severe. He then received one of the following treatments: 1. Placebo: lactose, plus acupuncture placebo 2. Codeine: codeine, plus acupuncture placebo 3. Acupuncture (Ho-Ku): lactose, plus 2 Ho-Ku points 4. Codeine-acupuncture: codeine, plus 2 Ho-Ku points. The pain intensity score was recorded by the observer at half-hour intervals for 3 hours. Patients in treatment groups 2, 3 and 4 showed significantly greater pain relief than those in treatment group 1. For the 1st half hour, there was more pain relief with Ho-Ku alone than with codeine plus Ho-Ko (p less than 0.01). However, for the 2, 2 1/2, and 3-hour periods, codeine plus Ho-Ku produced more pain relief than any of the other treatments.

Acupuncture Therapy↗
PubMed2002

The effect of codeine in anti-cough syrup on morphine screen.

BACKGROUND: Codeine is a lawfully permitted ingredient of over-the-counter cold and cough medicines readily available to the public in Taiwan. Drug abusers often use it as a substitute for morphine and heroin, attributing the morphine in the urine test to therapeutic cough medicine. In the literature, several criteria for taking codeine, using a single large-dose model, have been proposed. Here, we evaluate whether these criteria still fit in therapeutic situation. METHODS: Ten healthy volunteers each received, over two days, a total of 8 doses of cough syrup containing 4.5 mg of codeine phosphate per dose. Urine specimens were collected regularly during and in the 3 days after syrup consumption. The urine specimens were analyzed by an enzyme immunoassay screening test and a gas chromatography-mass spectrometry (GC-MS) confirmation test. RESULTS: Positive screen was noted during syrup use and 12-30 hours after the last dose of medication. The morphine:codeine ratio was < 1 during syrup use and 12 hour after the last dose of syrup. In only 1.4% of the urine specimens was the morphine:codeine ratio 1-3.0, and in these, the concentrations of morphine and codeine were both below 300 ng/mL. CONCLUSIONS: The results are compatible with the findings of the single large-dose model and may be used as a reference for the interpretation of urine analysis after the intake of multiple therapeutic doses of cough syrup with codeine.

Adult↗
PubMed1990

Skin prick test responses to codeine, histamine, and ragweed utilizing the Multitest device.

Epicutaneous skin testing is a useful diagnostic tool in evaluating allergic disorders. Utilizing the Multitest device, skin prick test responses to codeine phosphate, histamine phosphate, and ragweed were examined in 56 human subjects. Relationships between the two positive controls, codeine and histamine, and their use as a reference denominator for ragweed reactions were assessed. Ragweed elicited detectable wheals in 15/56. Histamine phosphate (2.75 mg/mL) elicited a positive wheal response in 52/56 subjects, while codeine phosphate elicited a positive wheal in 39/56 and 30/56 subjects at 30 and 3 mg/mL, respectively. Wheal sizes for codeine phosphate at both 30 and 3 mg/mL showed significantly concordant relationships with histamine phosphate-induced wheal sizes (Spearman rho, P = .0084 and .0155, respectively); however the intersubject coefficient of variation was lower for histamine-induced wheal sizes (44%) than for codeine-induced wheal sizes (64% and 65%, respectively for 30 and 3 mg/mL). When a ratio of allergen to positive control reaction size was used to grade ragweed reactions, different patterns were observed using codeine compared with histamine. These results have implications in utilizing codeine phosphate as a positive skin prick test control for allergy testing.

Adolescent↗
PubMedDate not supplied

Determination of codeine and morphine in human plasma by high performance liquid chromatography with serial electrochemical detection.

A method is described for the determination of codeine and its metabolite, morphine, at low nanogram concentrations in plasma. Analysis is accomplished by high-performance liquid chromatography utilizing a cyanopropyl normal bonded phase (NBP) column in reversed-phase mode and two electrochemical detectors in series configuration. Two internal standards are utilized, ethyl morphine for codeine and nalorphine for morphine. Codeine and morphine concentration data are presented for several patients receiving codeine-containing medications. The lower limit of detectability was 2.00 +/- 0.39 ng per mL for codeine and 1.20 +/- 0.83 ng per mL for morphine. The patient sample mean within-run coefficients of variation for codeine and morphine (at 10 ng per mL) were less than 10 percent, n = 30. The between-run coefficient of variation for codeine was also less than 10 percent (over a range of two to 190 ng per mL, n = 61), and was approximately 15 percent for morphine (over a range of two to 40 ng per mL, n = 31).

Chromatography, High Pressure Liquid↗
PubMed1986

Assessment of Fiorinal with Codeine in the treatment of tension headache.

A randomized, double-blind, placebo-controlled, multicenter study was conducted to ascertain the contribution of Fiorinal and codeine phosphate to the efficacy of Fiorinal with Codeine in relieving the pain, tension, and muscle stiffness associated with tension headache. Patients were given Fiorinal with Codeine, Fiorinal alone, codeine alone, or placebo for use during two separate headache attacks at least 24 hours apart and were asked to rate the effectiveness of the assigned medication on each occasion. The various symptoms of tension headache were evaluated by the patient 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. At the final patient visit, the investigator assessed the effect of treatment on the three chief components of tension headache, head pain, psychic tension, and muscle contraction. Fiorinal with Codeine was generally significantly more effective than placebo or Fiorinal alone in improving all patient-evaluated items between the second and the fourth hours after administration. The combination was also generally significantly better than codeine alone with respect to pain severity, pain relief, the ability to perform daily activities, and average pathology. The three variables rated by the physician also were generally reduced significantly more with the combination than with placebo or Fiorinal alone. Side effects occurred in only one patient treated with Fiorinal with Codeine.

Aspirin↗
PubMed1986

Ethanol inhibition of codeine and morphine metabolism in isolated rat hepatocytes.

Suspensions of isolated hepatocytes from male Wistar rats were prepared according to a two step Ca++-free collagenase perfusion method. Codeine, morphine or norcodeine were incubated with hepatocytes at 37 degrees C for up to 90 min in the absence and presence of ethanol. The elimination rate constant (Kel) of codeine and morphine was reduced with approximately one-third and one-fourth, respectively, in the presence of 60 mM ethanol, whereas the presence of ethanol did not alter the Kel of norcodeine significantly. The inhibition of codeine metabolism was dose-dependent, extending from approximately 15% at 10 mM ethanol to 40 to 50% at 100 mM. A 3-fold increase in the ratio of morphine concentration (formed from codeine) to the amount of codeine metabolized was observed in the presence of ethanol as compared to control cells. The mean morphine concentration was 170% higher in the ethanol-treated suspensions than in the controls. The ratio of norcodeine concentration to codeine metabolized was unchanged. The inhibition of morphine metabolism was accompanied by a similar reduction of morphine-3-glucuronide formation. The accumulation of morphine observed in the cell medium in the presence of ethanol might be due to inhibition of other metabolic pathways from codeine, thus shunting to morphine formation, combined with the inhibitory effect of ethanol on morphine metabolism per se.

Animals↗
PubMed1995

The efficacy and safety of moguisteine in comparison with codeine phosphate in patients with chronic cough.

We conducted a multicentre, double-blind, parallel group study to compare the clinical efficacy of a new antitussive drug, moguisteine (100 mg t.i.d.), to that of a reference standard, codeine (15 and 30 mg, t.i.d.). Both drugs were given orally for a period of two days. A group of 119 patients (mean age 54 yrs; 61 females and 58 males) with chronic, dry or slightly productive cough, associated with various respiratory disorders (including chronic obstructive pulmonary disease, respiratory malignancies and pulmonary fibrosis) were enrolled at six participating centres. The percentage reduction in the number of morning coughs over a period of 6 h after the first administered dose compared to baseline assessment, was 21% with moguisteine (n = 39), 28% with codeine 15 mg (n = 38), and 29% with codeine 30 mg (n = 36). Differences between treatments were not significant. The percentage reduction in the number of nocturnal coughs per hour, after the last evening dose compared to baseline assessment, was 33, 46 and 52%, respectively. Subjective assessments (patients' visual analogue scale scores of cough frequency, cough intensity and sleep disturbance, and investigators' ranking of cough severity) indicated that there was a similar improvement in cough symptoms in all treatment groups. Adverse events were observed in two patients on moguisteine, three on codeine 15 mg, and five on codeine 30 mg. No event was serious, but discontinuation of treatment was required in two patients on codeine 30 mg. The results of our study suggest that moguisteine 100 mg t.i.d. is safe, and seems to have an antitussive activity similar to that of codeine 15-30 mg t.i.d.

Administration, Oral↗
PubMed1994

The influence of pharmacogenetics on opioid analgesia: studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model.

In the Sprague-Dawley (SD) rat, the O-demethylation of codeine to morphine is catalyzed by cytochrome P4502D1 (CYP2D1), which is absent in the female Dark Agouti (DA) rat. Oxycodone is similar in structure to codeine but, in contrast, has an analgesic potency in humans similar to morphine. The aim of the study was to test whether the DA rat and the SD rat pretreated with the CYP2D1 inhibitor quinine showed attenuation in analgesia to codeine and oxycodone. With the use of the tail flick model, dose-response curves were constructed to codeine, morphine, oxycodone and oxymorphone (the O-demethylated metabolite of oxycodone) in both rat strains. Codeine did not induce analgesia in the DA rat and there was a 60% reduction in codeine analgesia in the SD rat pretreated with quinine in comparison to the untreated SD rat. In the DA rat, the ED50 to oxycodone was increased 10-fold but there was a significant (P = .0001) prolongation in the duration of analgesia in comparison to that in the untreated SD rat. In the quinine-pretreated SD rat, there was no reduction in oxycodone analgesia but the duration of analgesia was also prolonged. It was concluded that 1) codeine-mediated analgesia requires the formation of morphine through the functional activity of CYP2D1 and 2) oxycodone-mediated analgesia may only be partly dependent on CYP2D1.

Analgesia↗
PubMed1976

Antemortem conversion of codeine to morphine in man.

Forty-five drug overdose cases involving codeine were investigated. Concentrations of codeine and morphine were determined in blood, bile, liver, kidney, and urine. Ratios of codeine to morphine values for each of these specimens were compared and evidence was developed that codeine was metabolized partially into morphine in the antemortem stage. Morphine concentration was less than that of codeine in blood, liver, kidney, and urine. However, bile analyses showed that the amount of morphine exceeded that of codeine, suggesting a more active demethylation activity in the hepatic system than in the blood and other tissues studied. Controlled-in-vitro studies showed that no codeine demethylation occurred in postmortem tissues during cold storage for a period as long as 30 days.

Bile↗
PubMed2001

Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients.

Up to 1999 more opioid dependent patients in Germany were substituted with codeine or dihydrocodeine (summarised as codeine) than with methadone. The current retrospective study compares the differences in detoxification treatment outcome for codeine-substituted patients, methadone-substituted patients and patients injecting illicit heroin. The study is based on the medical records of 1070 patients admitted consecutively for opioid and polytox detoxification between 1991 and 1997. The main hypothesis was that injecting illicit-heroin users would complete detoxification treatment less often than codeine- or methadone- substituted patients, and that methadone-substituted patients who had received more structured treatment would complete more often than codeine-substituted patients who did not receive any structured treatment beyond the prescription of codeine. We analysed a number of demographic and drug related variables as possible predictors. Our bivariate analyses confirmed our main hypothesis: 50.4% (OR: 1.8) of the methadone-substituted patients, 45.5% (OR: 1.5) of the codeine-substituted patients and 35.9% (OR: 1 comparison group) of the injecting illicit-heroin users completed the detoxification program (P=0.006). This finding remained significant even after correcting for a number of confounders. Using stepwise multiple logistic regression analyses, we found age, education, history of imprisonment, regular contact with a counsellor, currently being on probation and reported plans for participating in an abstinence treatment program to be significant predictors of completing detoxification treatment. Although the current analysis did not rule out differences in pharmacological effects as a contributing factor, the results are consistent with an interpretation of a dose-response association between psychosocial/psychotherapeutic support and detoxification outcome. More psychosocial/psychotherapeutic support leads to better detoxification treatment response.

Adult↗
PubMed1976

Asprin and codeine in two postpartum pain models.

Aspirin and codeine, standard reference analgesics, are frequently used as positive controls in clinical trials of new oral analgesics. In randomized parallel double-blind studies, single doses of aspirin and codeine were compared with placebo in episiotomy pain (99 patients) and in postpartum uterine pain (130 patients), common models in analgesic trials. With aspirin, 600 and 1,200 mg, in episiotomy pain, analgesia as measured by pain intensity difference (PID) scores began within 1 hr, peaked at the second hour (p less than 0.01), and continued to the fifth hour (p less than 0.01). In uterine pain, responses with aspirin, 650 mg, were observed to be equally good. With codeine, 60 mg, in episiotomy pain measurable analgesia was present by the second hour and was significant at the fourth hour (p less than 0.05); in uterine pain, responses were indistinguishable from placebo throughout an 8-hr time-course. Codeine seemed ineffective and therefore umacceptable as a positive control in uterine pain. These data imply that the two postpartum pain models are qualitatively different: episiotomy pain seems sensitive to both aspirin and codeine, while uterine pain appears sensitive to aspirin but not to codeine.

Adult↗
PubMedDate not supplied

An appraisal of codeine as an analgesic: single-dose analysis.

Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult.

Acetaminophen↗