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PubMed2003

Codeine and morphine blood concentrations increase during blood loss.

During extensive blood loss, a plasma volume refill will take place by transfer of extravascular fluid into the circulation. Drugs present in this fluid may follow and cause a rise or a drop in blood drug concentration, depending on their levels and accessibility in the restoration fluid. This study explored the possible changes of codeine, and its metabolite morphine, in whole blood during a standardized exsanguination in the rat. Three doses containing 5 mg codeine were given orally. In eight rats, blood loss was accomplished by slowly withdrawing 0.8 mL blood at 10 min intervals during 70 min. In control rats, blood was withdrawn only at 0 and 70 min. At 70 min, the final/initial codeine and morphine concentration ratios were 0.70 +/- 0.38 and 0.88 +/- 0.47, respectively, in controls, but increased to 1.28 +/- 0.44 (p = 0.014) and 1.41 +/- 0.34 (p = 0.021), respectively, in exsanguinated rats. It is concluded that blood loss can affect blood drug concentrations.

Animals↗

PubMed2003

The detection of morphine and codeine in human teeth: an aid in the identification and study of human skeletal remains.

When studying unidentified putrefied or skeletonised human remains it may be difficult to obtain information on drug habits which may prove important for the construction of a biological profile or lead to hypotheses on the manner of death. The detection of morphine and codeine in teeth from human remains may prove crucial in obtaining such information and thus give forensic odontology and anthropology a further tool for identification. Because teeth can be an important deposit of exogenous substances accumulated both in the pulp and in the calcified tissues, they are an invaluable source of data from a toxicological point of view. The authors therefore tested 3 groups of teeth for morphine and codeine: the first group consisted of artificially aged teeth from individuals known to have died of heroin overdose; the second, of teeth from individuals with no history of drug abuse; the third, of teeth from cases of burnt, putrefied and skeletonised remains found in conditions strongly suggestive of a drug-related death. Results showed that in groups 1 and 3 morphine and codeine could still be identified in the teeth, proving that these tissues may be a reliable source for toxicological information concerning the history of the individual. Further studies are needed to verify whether the substances detected reflect drugs in circulation in an acute phase (and therefore present in blood vessels in the pulp) or whether they represent drugs which have percolated and been stored in dentine and enamel and thus denote a history of drug abuse. Nonetheless this study shows that teeth may be an important source of toxicological information in the forensic scenario.

Adult↗

PubMed1992

Robotic method for the analysis of morphine and codeine in urine.

A totally automated procedure has been developed for the detection and quantitation of morphine and codeine in urine case samples. The samples were initially screened for these drugs by a Syva EMIT Toxicology System (ETS). A Zymate laboratory robotic system confirms positive samples from Syva ETS by performing the hydrolysis, extraction, and derivatization of morphine and codeine. The derivatized morphine and codeine were detected using gas chromatography/mass spectrometry (GC/MS). Enzymatic hydrolysis conditions were experimentally optimized during method development. The automation of these procedures has proven to be reliable and efficient.

Codeine↗

PubMed1999

[Assay of diclofenac sodium and codeine phosphate in tablet by multiwavelength K-factor spectrophotometry].

Assay of diclofenac sodium and codeine phosphate in tablet is reported in this paper. The calibration curves were linear over the range of 11.18-25.40 microg/mL of diclofenac sodium and over the range of 6.785-15.42 microg/mL of codeine phosphate. The average recoveries and relative standard deviations of diclofenac sodium and codeine phosphate were 100.1%, 0.36% and 100.7%, 0.80%, respectively. The method is simple and rapid, and the results are satisfactory.

Codeine↗

PubMedDate not supplied

In vivo formation of codeinone and morphinone from codeine. Isolation and identification from guinea pig bile.

Codeinone (CO) and morphinone (MO) were isolated and identified in the bile of guinea pigs given sc injections of codeine. Authentic CO was synthesized and characterized by the NMR and mass spectra of its 2-mercaptoethanol (ME) adduct. This material was then used as the standard to identify the CO-ME adduct in the bile of codeine-treated animals. The MO-ME adduct was also identified in the bile with authentic materials prepared earlier. The results of our investigations indicated that 10.5 and 2.7% dose of CO and MO, respectively, were produced for 6 hr after the codeine was given. The metabolites were separated by preparative HPLC on a reverse phase column packed with C18 gel using a 10 mM sodium phosphate buffer, pH 6.8/CH3CN, 1:1 (v/v) as an eluate. For the further purification of metabolites, we used another reverse phase column with the same mobile phase. A structural elucidation of the ME adduct of metabolites was then performed by fast atom bombardment mass spectroscopy and 400 MHz fourier transform-NMR spectrometric analysis, and identified as (8S)-(2-hydroxyethylthio)dihydrocodeinone and (8S)-(2-hydroxyethylthio)dihydromorphinone, respectively.

Animals↗

PubMed1990

Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain.

Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications.

Acetaminophen↗

PubMed1986

Comparison of diflunisal and acetaminophen with codeine in the management of grade 2 ankle sprain.

The emergency physician treats many patients with mild to moderate pain due to musculoskeletal injury. The physician must consider the extent of injury, the patient's medication history, and the potential for abuse when prescribing an oral analgesic. A study was designed to compare the efficacy of two oral analgesics, one containing a narcotic and one nonnarcotic, in relieving mild to moderate pain associated with grade 2 ankle sprain. Forty patients were enrolled--all with moderate pain--and were randomly allocated to treatment with either diflunisal or acetaminophen with codeine. Both analgesic agents were equally effective in relieving the pain. Side effects were experienced by six patients, all of whom were receiving acetaminophen with codeine; none of the patients given diflunisal noted side effects. Global assessments of the efficacy and tolerability of the study drugs showed that 89% of 19 patients given diflunisal and 43% of 21 patients given acetaminophen with codeine considered their respective analgesics excellent or very good.

Acetaminophen↗

PubMed1985

Scarlatiniform rash and urticaria due to codeine.

Scarlatiniform rash and urticaria were observed twice in the same patient following codeine intake. This rare drug-induced eruption may lead to mis-diagnosis in patients taking mild analgesics containing codeine. The side effects of codeine, hypersensitivity mechanisms, and the use of analgesic combination products are discussed.

Adult↗

PubMed1987

Double-blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy.

Meclofenamate sodium, a nonsteroidal anti-inflammatory agent, was compared at two dose levels (100 mg and 200 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 218 women after normal vaginal delivery. The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain. Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity. The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain. Adverse experiences with the study medications were minimal (6.4%). Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium. Meclofenamate sodium is a safe, effective analgesic for acute episiotomy pain.

Adolescent↗

PubMed1987

Comparison of meclofenamate sodium with codeine and placebo for the treatment of episiotomy pain.

Meclofenamate sodium, a nonsteroidal anti-inflammatory drug with proven analgesic effects, was compared at two dose levels (200 mg and 100 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 327 women experiencing episiotomy pain after normal delivery. Meclofenamate sodium at either dose was significantly better than codeine or placebo in reducing pain intensity and increasing pain relief, and it had a longer duration of action. Adverse effects were minimal, and their frequency did not differ significantly among treatment groups. Meclofenamate sodium appears to be as safe as and more effective than codeine for the management of episiotomy pain.

Adolescent↗

PubMed1985

Acetylsalicylic acid compared with acetylsalicylic acid plus codeine as postoperative analgesics after removal of impacted mandibular third molars.

In a multicenter, double blind clinical trial a combination of acetylsalicylic acid 500 mg + codeine phosphate 30 mg has been compared with acetylsalicylic acid 500 mg as postoperative analgesics in patients with pain after surgical removal of impacted mandibular third molars. Evaluation of the results from 129 patients showed that the combination of acetylsalicylic acid and codeine provided better pain relief and also the number of tablets used was smaller and the time intervals between repeated doses were longer than with acetylsalicylic acid only. Adverse effects were few and similar for both drugs. It may be concluded that the combination of 500 mg acetylsalicylic acid and 30 mg codeine phosphate provides a useful analgesic for more severe pain conditions in oral surgery.

Adolescent↗

PubMed1985

[The bioavailability of combination preparations of acetylsalicylic acid and codeine phosphate].

Plasma levels time curves of acetylsalicylic acid, salicylic acid, salicyluric acid and codeine were monitored after intravenous, oral and rectal application (single dose) of preparations containing acetylsalicylic acid and codeine. The mean absolute bioavailability of acetylsalicylic acid was 68% after oral application and 60% after rectal application. The corresponding bioavailability data of codeine were 59% and 63%, respectively.

Administration, Oral↗

PubMed1985

Acute toxicity and analgesic action of a combination of buclizine, codeine and paracetamol ('Migraleve') in tablet and suppository form in rats.

Studies in rats were carried out to determine the acute toxicity and analgesic effect of a combination preparation ('Migraleve') containing codeine and paracetamol and the individual analgesics when given orally or by rectal administration. The results showed that the combination was no more toxic than paracetamol alone and, on the basis of the LD50:ED50 ratio, was less toxic by the oral than by the rectal route. In the rat-tail test, the combination induced a well-defined dose-dependent analgesic response which was greater after rectal administration. Codeine and paracetamol tested individually were effective only at relatively high dosage and, like the combination, their analgesic effects were greater after rectal administration and more clearly dose-dependent than after oral administration. Comparison of the area under the time-effect curves for the combination and the individual components confirmed the synergism between codeine and paracetamol.

Acetaminophen↗

PubMed1984

[Bioavailability of codeine and paracetamol in a combination preparation following oral and rectal administration].

The plasma concentrations of acetaminophen (paracetamol) and codeine were determined in a cross-over study in twelve healthy volunteers after oral and rectal application of a compound preparation. The relative bioavailability from the two forms of application was also computed. The two active substances showed almost parallel plasma concentration paths, and thus were systemically available at the same time. The maximum levels in plasma were already reached after one to two hours. In both active substances the suppositories displayed a classical retardation effect. In contrast to acetaminophen the rectal absorption of codeine was almost as effective as the oral absorption. Thus this application form shows almost bioequivalency vis-à-vis the capsule form. Based on these results the rectal form of administration of codeine as well as the combination of this substance with acetaminophen can be regarded, from the pharmacokinetic point of view, as a rational enhancement of the treatment of various forms of pain.

Acetaminophen↗

PubMed1981

Zomepirac sodium vs APC with codeine for oral surgery pain.

In this double-blind, repeat-dose study, 323 outpatients with moderate to severe pain after oral surgery assessed zomepirac sodium, a new oral, single-entity, nonnarcotic analgesic, and APC with codeine, 30 mg, a reference standard. Pain relief obtained with 100 mg of zomepirac sodium was significantly superior to that of APC with codeine, 30 mg; 50 mg of zomepirac sodium was as effective as the reference drug. The analgesic acceptability was highest for 100 mg of zomepirac sodium. Both doses of this new drug produced significantly fewer adverse reactions than APC with codeine, 30 mg.

Aspirin↗

PubMed1980

Four cases of recurrent pseudo-scarlet fever caused by phenathrene alkaloids with a 6-hydroxy group (codeine and morphine).

Four patients with a clinical picture resembling that of scarlatina are described. This clinical picture was found to be based on a delayed-type allergy for codeine and morphine. Investigation showed that the codeine or morphine allergy is essentially dependent on the hydroxyl group at the 6 position of the basic phenanthrene structure but only when this group is bound equatorially, as is the case for codeine and morphine.

Adult↗

PubMedDate not supplied

Effective treatment of narcolepsy with codeine in a patient receiving hemodialysis.

A 64-year-old man with narcolepsy could not take stimulant drugs due to coronary heart disease. In the past he noted improvement in alertness when taking codeine for pain, but this was eventually discontinued. After he developed end-stage renal disease, and because the use of stimulants in this setting may be difficult, treatment with codeine was again initiated. This resulted in dramatic improvement in alertness and substantial reduction of cataplexy. Because it is simple to use and familiar to most physicians, codeine may be the drug of choice for narcoleptic patients who are undergoing hemodialysis.

Codeine↗

PubMed1996

Pharmacokinetics and drug input characteristics for a diclofenac-codeine phosphate combination following oral and rectal administration.

In a single dose cross-over study with 12 healthy male volunteers the plasma concentrations of diclofenac (CAS 15307-86-5) and codeine (CAS 76-57-3) were determined after oral and rectal application of formulations containing 50 mg of each drug. For kinetic analysis of the concentration-time profiles non-compartmental as well as compartmental procedures were used. The compartment model included two disposition compartments supplemented by a dissolution and drug absorption step. For both compounds, the AUC0-infinity values of the two treatments were similar with only a slightly higher AUC for the suppositories, which was not found to be significantly different under the employed conditions (p > 0.05). Referring to the pharmacokinetic parameters Cmax and tmax typical differences between oral and rectal formulations were observed. For the suppositories, diclofenac and codeine average peak plasma concentrations were only half as high as for the tablets, whereas the respective tmax values were doubled. The results obtained show a similar extent of diclofenac and codeine bioavailability for both administration routes, but the rate of drug input was lower for the suppositories. The total mean input time (MITtot) was found to be significantly longer for the suppositories. This seems to be caused by a slow release from the dosage form or dissolution of the drugs, which is confirmed by a longer MITtot compared to the MRTsys in most of the volunteers.

Administration, Oral↗