SEARCH · PubMed Health

Results for “Codeine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 451 records · Page 25Linked to original sources

PubMed1998

Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain.

A prospective double-blind randomized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25 mg t.i.d.). All demographic and clinical characteristics including cancer type, presence of bone metastases, baseline pain severity, neuropathic and nociceptive pain, and depressive state, were well balanced between the three treatment groups. The main analysis of the study was on the VAS scores at visit 2 (day 4). The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac. Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy, while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events. In conclusion, in a short-term evaluation the addition of a tricyclic anti-depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone.

Administration, Oral↗

PubMed1986

Simultaneous determination of codeine and chlorpheniramine in human plasma by capillary column gas chromatography.

A specific and highly sensitive capillary column gas chromatographic method was developed for the simultaneous determination of codeine and chlorpheniramine in human plasma. The method involves a solvent extraction and analysis by capillary column gas chromatography on a cross-linked 50% phenylmethyl silicone fused-silica capillary column with flame thermionic detection. A 10% solution of n-butanol in toluene was used as extraction medium and pyrilamine was used as internal standard. Reproducibility, linearity of calibration curves and specificity were all satisfactory with both drugs. The plasma concentration of codeine and chlorpheniramine could be measured at levels down to 0.9 ng/ml as codeine phosphate and 0.4 ng/ml as chlorpheniramine maleate, respectively. The method was applied to plasma samples from normal volunteers, and was confirmed to be adequate for biopharmaceutical and pharmacokinetic studies.

Adult↗

PubMed1999

Highly sensitive gas chromatographic-tandem mass spectrometric method for the determination of morphine and codeine in serum and urine in the femtomolar range.

A sensitive and specific method was developed for the determination of codeine and morphine in human serum and for the determination of trace amounts of endogenous morphine in human urine. The analytes were recovered from serum by a simple liquid-liquid extraction method. Urine samples were hydrolyzed, and purified by two liquid-liquid extraction steps and a solid-phase extraction. Samples were derivatized to the pentafluoropropionic esters and measured by gas chromatography tandem mass spectrometry. Using the deuterated analogues as internal standards a limit of quantification of 20 fmol/ml (5.7 pg/ml) morphine and 500 fmol/ml (150 pg/ml) codeine in human serum and of 2.5 fmol/ml (0.71 pg/ml) morphine in urine was achieved. The method was suitable for the determination of morphine and codeine in pharmacokinetic studies and for the determination of the urinary excretion of endogenous morphine.

Calibration↗

PubMed2001

LC method for the analysis of paracetamol, caffeine and codeine phosphate in pharmaceutical preparations.

An accurate, simple, reproducible and sensitive method for the determination of paracetamol, caffeine and codeine phosphate has been developed and validated. Paracetamol, caffeine and codeine phosphate were separated using a muBondapack C8 column by isocratic elution with flow rate 1.0 ml/min. The mobile phase composition was 420/20/30/30 (v/v/v/v) 0.01 M KH2PO4, methanol, acetonitrile, isopropyl alcohol and spectrophotometric detection was carried out at 215 nm. The linear range of detection for paracetamol, caffeine and codeine phosphate were between 0.400 and 1500 microg/ml; 0.075 and 90 microg/ml; 0.300 and 30 microg/ml, respectively. The method has been shown to be linear, reproducible, specific, sensitive and rugged.

Acetaminophen↗

PubMed2002

Determination of codeine in urine and drug formulations using a clay-modified screen-printed carbon electrode.

Both flow-injection analysis and square-wave stripping voltammetry were evaluated for the determination of codeine in pharmaceutical formulations using a nontronite clay-modified screen-printed carbon electrode. Compared with a bare screen-printed carbon electrode, the nontronite clay-modified screen-printed carbon electrode exhibited a marked enhancement of the current response of codeine. A linear calibration plot was obtained over the 2.5-45 microM range (correlation coefficient=0.999) in pH 6.0 phosphate buffer solution with a detection limit of 20 nM (S/N=3) by square-wave voltammetry (SWV). While, in flow-injection analysis, the linearity was over 5-120 ng range with a detection limit of 1 ng in 20 microl loop. The nontronite clay-modified screen-printed carbon electrode can be either disposable or reused since the renewal gave a good reproducible surface. Quantitative analysis was performed by the standard addition method for codeine content in both urine and commercially available drugs.

Adult↗

PubMed2001

Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers taking codeine.

INTRODUCTION: Constipation is a common side-effect of opioid therapy; in addition to their analgesic effect, opioids reduce intestinal secretion and motility with an increase in whole-gut transit time. Naloxone, a specific opioid antagonist, reverses these effects but may also cause symptoms of opioid withdrawal in patients on long-term therapy. AIM: To use an enteric-release formulation, designed to produce a topical effect in the gut, with minimum systemic effects. METHODS: Naloxone 10 mg b.d. and codeine 30 mg b.d. were used with identical placebo capsules in four sets of studies; 12 male volunteers were given the drugs alone and in combination, with a control study involving double placebo, during each of four study periods. Whole-gut transit time was calculated and compared for each treatment period. RESULTS: Naloxone, both alone and with codeine, significantly shortened the mean whole-gut transit time compared with the control period, respectively, from 53.1 to 42.1 h (P=0.005) and to 40.7 h (P=0.024). Urgency to defecate was reported by two volunteers on naloxone alone and by three on combination therapy. CONCLUSIONS: The results show that the naloxone formulation counteracts the effect of codeine on intestinal transit, suggesting that it may have useful clinical applications.

Administration, Oral↗

PubMed1999

Comparison of morphine sulphate and codeine phosphate in children undergoing adenotonsillectomy.

We undertook a double-blind study to evaluate equianalgesic doses of intramuscular morphine sulphate (0.15 mg.kg-1) and codeine phosphate (1.5 mg.kg-1) in 40 healthy children undergoing adenotonsillectomy. There were no significant differences in pain scores, analgesic requirements or sedation scores between the two groups over the following 24 h. More children vomited in the morphine group (60%) than the codeine group (30%) between one and six h after the procedure (P < 0.05). Codeine phosphate is associated with less postoperative vomiting than morphine sulphate while providing comparable postoperative analgesia for adenotonsillectomy.

Adenoidectomy↗

PubMed2004

Codeine intoxication associated with ultrarapid CYP2D6 metabolism.

Life-threatening opioid intoxication developed in a patient after he was given small doses of codeine for the treatment of a cough associated with bilateral pneumonia. Codeine is bioactivated by CYP2D6 into morphine, which then undergoes further glucuronidation. CYP2D6 genotyping showed that the patient had three or more functional alleles, a finding consistent with ultrarapid metabolism of codeine. We attribute the toxicity to this genotype, in combination with inhibition of CYP3A4 activity by other medications and a transient reduction in renal function.

Analgesics, Opioid↗

PubMed1986

Presence and formation of codeine and morphine in the rat.

Endogenous codeine and morphine were identified in rat brain by immunological determination following HPLC. To demonstrate occurrence of a biosynthetic pathway to morphine in mammals similar to that used by the poppy plant, (+)-salutaridine, (-)-thebaine, and (-)-codeine were administered to rats intravenously. These compounds, which are intermediates in the synthesis of morphine in Papaver somniferum, caused a marked increase in the codeine and morphine levels in rat tissues. This provides evidence for a biosynthetic pathway to morphine in mammalians.

Animals↗

PubMed2004

A frameshift mutation and alternate splicing in human brain generate a functional form of the pseudogene cytochrome P4502D7 that demethylates codeine to morphine.

A frameshift mutation 138delT generates an open reading frame in the pseudogene, cytochrome P4502D7 (CYP2D7), and an alternate spliced functional transcript of CYP2D7 containing partial inclusion of intron 6 was identified in human brain but not in liver or kidney from the same individual. mRNA and protein of the brain variant CYP2D7 were detected in 6 of 12 human autopsy brains. Genotyping revealed the presence of the frameshift mutation 138delT only in those human subjects who expressed the brain variant CYP2D7. Genomic DNA analysis in normal volunteers revealed the presence of functional CYP2D7 in 4 of 8 individuals. In liver, the major organ involved in drug metabolism, a minor metabolic pathway mediated by CYP2D6 metabolizes codeine (pro-drug) to morphine (active drug), whereas norcodeine is the major metabolite. In contrast, when expressed in Neuro2a cells, brain variant CYP2D7 metabolized codeine to morphine with greater efficiency compared with the corresponding activity in cells expressing CYP2D6. Morphine binds to micro-opioid receptors in certain regions of the central nervous system, such as periaqueductal gray, and produces pain relief. The brain variant CYP2D7 and micro-opioid receptor colocalize in neurons of the periaqueductal gray area in human brain, indicating that metabolism of codeine to morphine could occur at the site of opioid action. Histio-specific isoforms of P450 generated by alternate splicing, which mediate selective metabolism of pro-drugs within tissues, particularly the brain, to generate active drugs may play an important role in drug action and provide newer insights into the genetics of metabolism.

Alternative Splicing↗

PubMed2002

Comparative biotransformation of morphine, codeine and pholcodine in rat hepatocytes: identification of a novel metabolite of pholcodine.

1. Pholcodine (3-morpholinoethylmorphine), a semi-synthetic alkaloid, is widely used as an antitussive agent. 2. Norpholcodine [7,8-didehydro-4,5alpha-epoxy-3-(2-morpholinoethoxy)morphinan-6alpha-ol] (NP) and pholcodine-N-oxide [1(9a)-dehydro-(4aR,5S,7aR,9cS,12S)-4a,5,7a,8,9,9a-hexahydro-5-hydroxy-12-methyl-3-morpholinoethoxy-1H-8,9,c-(iminoethano)phenanthro[4,5-bcd] furan-12-oxide] (PNOX) were identified in incubations of pholcodine with freshly isolated rat hepatocytes by liquid chromatography/electrospray-mass spectrometry (LC/ESI-MS). 3. Synthesized NP and PNOX were characterized by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. 4. N-oxidation was the major metabolic pathway for pholcodine, producing a previously unreported metabolite. 5. The metabolism of morphine and codeine was also determined using freshly isolated hepatocytes. 6. For morphine, 3-glucuronidation was the major metabolic pathway, whilst for codeine it was dealkylation (O- and N-). 7. Neither morphine nor its metabolites were metabolites of pholcodine. 8. This observation supports the hypothesis that the absence of analgesic activity with pholcodine may be due to less O-dealkylation in vivo. 9. Together with the slow biotransformation of pholcodine (k(met) = 0.021 microM min(-1)) in comparison with morphine (k(met) = 0.057 microM min(-1)) and codeine (k(met) = 0.112 microM min(-1)), the results obtained were consistent with its low addiction potential and suggest that its antitussive efficacy is mediated by the parent drug or one of its metabolites other than morphine.

Analgesics, Opioid↗

PubMed1988

Changes in pupil diameter after oral administration of codeine.

Pupillary constriction occurs following administration of opioids and may be used as a marker of opioid activity. We have measured plasma concentrations and pupil diameters in 16 healthy volunteers after the oral administration of placebo or codeine. Pupil size decreased significantly after codeine compared with placebo. Pupil size was related to the plasma concentrations of codeine (P less than 0.05).

Administration, Oral↗

PubMedDate not supplied

A closer look at acetyl and pentafluoropropionyl derivatives for quantitative analysis of morphine and codeine by gas chromatography/mass spectrometry.

PFPA and acetic anhydride derivatives of morphine and codeine were evaluated with respect to stability, chromatography, potential for analytical interferences by other opiates, and suitability of major fragment ions for analysis by GC/MS with deuterated internal standards and selected ion monitoring (SIM). The PFPA derivatives showed acceptable stability and could be analyzed without interference from other opiates, but the codeine derivative had relatively poor chromatography and its mass spectrum had only two ions suitable for SIM. The acetic anhydride derivatives were stable and chromatographed well, but diacetyl hydromorphone enol, a minor product of derivatization of hydromorphone, interfered with analysis of morphine. 3-Monoacetylmorphine, a minor product of derivatization of morphine, prevented use of the abundant m/z 285 ion of derivatized D3-codeine as a qualifying ion in quantitative assays. The acetic anhydride derivative of morphine cannot be distinguished from the corresponding derivative of the heroin metabolite 6-monoacetylmorphine.

Acetic Anhydrides↗

PubMedDate not supplied

The certification of morphine and codeine in a human urine standard reference material.

The National Institute of Standards and Technology (NIST, formerly the National Bureau of Standards) has developed and certified a Standard Reference Material, SRM 2381, for use in testing for bias in determinations of morphine and codeine in human urine. Each unit of this SRM consists of three vials with different levels of morphine and codeine in lyophilized urine. Three different analytical methods, employing GC/MS, LC/MS, and MS/MS, were used to certify the concentrations of each analyte. Results from the three methods were in good agreement and, therefore, were statistically combined to yield certified values of 138, 293, and 578 ng/mL for morphine and 134, 283, and 591 for codeine. A round-robin study on this material among nine military laboratories demonstrated the suitability of the SRM for its intended purpose.

Chromatography, Liquid↗

PubMedDate not supplied

Hydromorphone and hydrocodone interference in GC/MS assays for morphine and codeine.

The specificity of a GC/MS assay of morphine and codeine was examined with particular regard to the potential interference due to hydromorphone and hydrocodone, compounds that cross-react extensively in opiate screening tests. A GC/MS method with solid-phase extraction and acetylation or trimethylsilylation was used. The equilibrium between keto and enol forms of the potential interferents was evaluated. Sodium borohydride was tried as a means for converting potential interferents into products that are more clearly separated from morphine and codeine. It was found that borohydride reduction proceeded easily and led to products that could be distinguished from morphine and codeine. Moreover, the quantitation of morphine in the presence of hydromorphone was improved if the borohydride step was included in the analysis.

Acetylation↗

PubMed2000

The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration.

This study investigated the disposition patterns of cocaine and opiates into hair and fingernail specimens collected from 8 volunteers enrolled in a 10-week inpatient clinical study. All subjects were African-American males with a confirmed drug use history. Scalp hair and fingernail scrapings were collected weekly throughout the course of the study. Head hair was collected from the posterior vertex region, and fingernail scrapings were collected along the entire ventral surface of the nail plate. The specimens were introduced to successive decontamination washes including an isopropanol wash and three phosphate buffer washes. All decontamination washes were collected and analyzed. All specimens were enzymatically digested prior to being subjected to solid-phase extraction and derivatization. Analyses were performed using electron impact gas chromatography-mass spectrometry. Analytes investigated included eight cocaine analytes and five codeine analytes. The limit of quantitation for all analytes ranged from 0.1 to 0.5 ng/mg for both matrices. Cocaine was present at the highest concentrations of any analyte in both hair and nail. Benzoylecgonine and ecgonine methyl ester were the primary metabolites in both matrices and were typically less than 15% of cocaine concentrations. Codeine was the only opiate analyte identified in either hair or nail. Observed drug disposition profiles were different for hair and nails. A significant dose-response relationship was observed for hair specimens. The mean peak concentrations in hair after low dosing were half the concentration observed after high-dose administration. Generally, no clear relationship was evident between nail drug concentrations and dose. Decontamination washes removed less than 20% of the total drug present in hair, but removed most of the drug concentrations (60-100%) in nail. This investigation demonstrated that higher concentrations of drug were found in the subjects' hair than in their fingernails and that cocaine was found in both matrices at a greater concentration than codeine. Although both hair and nail have similar physical and chemical properties and may share common mechanisms of drug incorporation, this clinical study suggests that there are distinct differences in their disposition profiles.

Area Under Curve↗

PubMed2001

Quantitation of morphine and codeine in human urine using high-filed asymmetric waveform ion mobility spectrometry (FAIMS) with mass spectrometric detection.

Morphine and codeine have been identified and measured in a human urine matrix using high-field asymmetric waveform ion mobility spectrometry (FAIMS) in a tandem combination with electrospray ionization (ESI) and mass spectrometric (MS) detection. The addition of helium to the nitrogen carrier gas resulted in a substantial improvement in the sensitivity of the ESI-FAIMS-MS instrument for the determination of morphine and codeine. Limits of detection in human urine were 60 ng/mL for morphine and 20 ng/mL for codeine with no clean-up, derivatization, or chromatographic separation of the sample prior to analysis.

Codeine↗

PubMed2005

Multiple aspects of hair analysis for opiates: methodology, clinical and workplace populations, codeine, and poppy seed ingestion.

Levels of morphine, 6-monoacetylmorphine (MAM) and codeine in hair in both clinical and workplace subjects are presented. Aggressive wash procedures, consisting of 1 isopropanol wash, three 30-min, and two 1-h buffer washes, followed by digestion, extraction and confirmation of digested samples, resulted in values from the cutoff of 2 ng morphine/10 mg hair to greater than 200 ng/10 mg hair. Both morphine and MAM were present above the cutoff in all hair samples from 69 clinical subjects. Only 39 of the 69 heroin-using subjects had urine tests positive for 6-MAM. In a study of morphine in hair following poppy seed consumption, ten subjects ingested 150 g of poppy seed over 3 weeks. Urine samples were collected on the days of poppy seed ingestion and hair samples were taken in the 5th week of the study. The range among the 10 subjects of the highest urine value for each subject was 2929 to 13,827 ng morphine/mL. Hair morphine levels were 0.05-0.48 ng/10 mg hair (average 0.17 ng/10 mg hair). Hair opiate levels of workplace subjects ranged somewhat lower than those of clinical subjects. While all clinical hair samples contained MAM, many workplace samples did not. From workplace samples, a maximum amount of morphine likely to be present from codeine use was 0-3.7% of the codeine in the hair.

Adult↗