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 217 records · Page 12Linked to original sources

PubMed1990

Codeine in analgesic doses does not depress respiration in patients with severe chronic obstructive lung disease.

Nineteen normocapnic patients with chronic obstructive lung disease participated in an open single dose safety study (part one) followed by a randomized double-blind cross-over study comparing two seven-days treatment periods of 1 g of paracetamol t.i.d. with 60 mg of codeine plus 1 g of paracetamol t.i.d., respectively (part two). In part one, continuous monitoring after a single dose of 2 g of paracetamol and 120 mg of codeine revealed no deterioration in the respiration and gas tensions. In part two, respiratory parameters and arterial gas tensions were recorded one hour after the last morning dose. PaCO2 increased insignificantly (0.05 less than P less than 0.10) by a median of 0.38 kPa during treatment with codeine and paracetamol compared to treatment with paracetamol alone. PaO2 decreased by 0.12 kPa (P greater than 0.10). There was no correlation between changes in PaCO2 and changes in PaO2. FVC, FEV1 and dyspnoea at rest were unchanged. Gastrointestinal side effects were reported significantly (P less than 0.02) more often during treatment with codeine plus paracetamol. There was no correlation between the plasma concentration of codeine or morphine and changes in respiratory parameters or adverse effects. The limitation for the short time clinical use of codeine as an analgesic to normocapnic patients with severe chronic obstructive lung disease in stable phase seem to be gastrointestinal side effects.

Acetaminophen↗

PubMed1990

Effect of codeine on the sensations elicited by loaded breathing.

The present study examined the effect of codeine, a centrally acting opiate, on the respiratory sensations elicited in normal subjects by breathing to exhaustion against externally applied inspiratory threshold loads. Subjects were tested on two separate days following the double-blind, randomized administration of either placebo or codeine (90 mg). The intensity of the sensations of effort and discomfort experienced during two loaded breathing trials (a "high" load that was 73% of the maximum inspiratory pressure (MIP) and a "low" load that was 63% of the MIP) was evaluated using category (Borg) scores on each day of study. To verify that the dosage of codeine administered was sufficient to produce analgesia, we also determined the effect of this dosage on the time that subjects could tolerate immersion of one hand in ice water. Codeine altered neither the perceived effort nor the sense of discomfort associated with breathing against external loads and had no appreciable effect on the time to exhaustion during loaded breathing trials. This dose of codeine did, however, increase the time that ice water immersion could be tolerated and reduced the rate at which the sense of discomfort increased over time during ice water trials. These results indicate that, provided the pressure-time index of respiratory muscle contraction remains constant, analgesic doses of codeine alter neither the sensations elicited by loaded breathing nor the total time that breathing against a fatiguing inspiratory load can be tolerated.

Adult↗

PubMed1982

Studies of the mechanism of the antidiarrheal effect of codeine.

To determine whether the antidiarrheal action of opiate drugs in humans is due to enhanced intestinal absorption rates, as suggested by recent experiments in animals, or is due to altered intestinal motility, as traditionally thought, we studied the effect of therapeutic doses of codeine on experimental diarrhea and on the rate of intestinal absorption of water and electrolytes in normal human subjects. Our results show that codeine (30-60 mg i.m.) markedly reduced stool volume during experimental diarrhea induced by rapid intragastric infusion of a balanced electrolyte solution. There was, however, no evidence that codeine stimulated the rate of intestinal absorption in the gut as a whole or in any segment of the gastrointestinal tract, either in the basal state or when absorption rates were reduced by intravenous infusion of vasoactive intestinal polypeptide. We also measured segmental transit times to determine whether and where codeine delayed the passage of fluid through the intestine. Codeine caused a marked slowing of fluid movement through the jejunum, but had no effect on the movement of fluid through the ileum or colon. In other studies, we found that the opiate antagonist naloxone did not significantly affect water or electrolyte absorption rates in the jejunum or ileum. We conclude (a) that therapeutic doses of codeine increase net intestinal absorption (and thereby reduce stool volume) by increasing the contact time of luminal fluid with mucosal cells, not by increasing the rate of absorption by the mucosal cells; and (b) that endogenous opiates do not regulate intestinal absorption in humans.

Adult↗

PubMed1993

Codeine and the breastfed neonate.

Codeine is an analgesic commonly used to relieve pain in the early post partum. Its metabolite, morphine, is probably responsible for its effectiveness in this use. However, morphine may also cause neonatal apnea. We studied free codeine and morphine levels in breastmilk of 17 samples from seven mothers and neonatal plasma of 24 samples from 11 healthy, term neonates. Levels were determined by radioimmunoassay. Milk codeine levels ranged from 33.8 to 314 ng/ml 20 to 240 minutes after codeine; morphine levels ranged from 1.9 to 20.5 ng/ml. Infant plasma samples one to four hours after feeding had codeine levels ranging from < 0.8 to 4.5 ng/ml; morphine ranged from < 0.5 to 2.2 ng/ml. Low infant plasma levels are secondary to low excretion into milk and the small amounts of milk available in the first few days. Moderate codeine use during this time (< or = four 60 mg doses) is probably safe.

Breast Feeding↗

PubMed1999

Codeine concentration in hair after oral administration is dependent on melanin content.

BACKGROUND: Analysis of drugs in hair has been used on a qualitative basis to estimate earlier exposure to drugs. Clinical applications are rare because of the lack of dose-response relationships in the studies performed to date, and questions remain regarding the mechanisms of drug incorporation into hair. Several human studies have shown differences in drug accumulation between pigmented and nonpigmented hair. However, the melanin concentration in hair was not determined and correlated to the amount of drug incorporated. METHODS: Nine human subjects were given codeine as a single oral dose, and plasma codeine concentrations were determined for 24 h, using gas chromatography-mass spectrometry. Hair samples were obtained weekly for a month. Total melanin, eumelanin, and codeine were measured quantitatively in hair samples by spectrophotometry, HPLC, and gas chromatography-mass spectrometry, respectively. RESULTS: There was an exponential relationship between codeine and melanin concentrations in hair, (r(2) = 0.95 with total melanin and r(2) = 0.83 with eumelanin). After normalizing the results by the area under the curve for codeine in plasma, we obtained r(2) = 0.86 for codeine vs total melanin and r(2) = 0.90 vs eumelanin. CONCLUSIONS: Our results stress the importance of melanin determination when measuring drugs in hair. We postulate that analysis of drug concentration in hair may be worthwhile in the monitoring of drug compliance if the results are normalized for melanin content.

Chromatography, High Pressure Liquid↗

PubMed2000

In vitro interaction of codeine and diclofenac.

There is very limited knowledge about possible pharmacokinetic interactions between opioid analgesics and nonsteroidal antiinflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain. The major metabolic pathway of the weak opioid codeine is glucuronidation to codeine-6-glucuronide. Therefore we investigated the influence of the NSAID diclofenac on the formation of codeine-6-glucuronide in vitro, using human liver tissue homogenate. The formation of codeine-6-glucuronide exhibited single enzyme Michaelis-Menten kinetics with an average V(max) of 93.6 +/- 35.3 pmol/mg/min. A noncompetitive inhibition of codeine-6-glucuronidation by diclofenac was observed with an average K(i) of 7.9 microM. These in vitro findings suggest that a pharmacokinetic interaction occurs in vivo, which has to be confirmed by an interaction study in human subjects. It can be speculated that in case of inhibition of glucuronidation, the amount of codeine available for other pathways especially O-demethylation to morphine is increased, resulting in higher morphine serum levels and therefore higher analgesic efficacy.

Aged↗

PubMed1989

Bioavailability study of fosfosal and codeine administered alone or in combination.

Fosfosal (2-phosphonoxybenzoic acid) is a new salicylic acid derivative which is used for treating inflammatory disease as well as in analgesic therapy. On the other hand, codeine together with acetylsalicylic acid is widely used in patients who require analgesic treatment for mild to moderate pain. The present study was carried out in ten healthy subjects to assess the pharmacokinetic profiles of single oral doses of fosfosal (1,200 mg) and codeine (30 mg) when administered alone or in combination. Blood samples were drawn on each study day and salicylic acid and codeine plasma concentrations were determined by HPLC and enzyme immunoassay methods, respectively. Individual pharmacokinetic parameters were calculated according to standard procedures and the magnitude and rate of bioavailability were tested using a 95% confidence internal approach. Results indicated no statistical differences in any of the kinetic parameters studied except for tmax values which were higher for fosfosal combined with codeine (2 +/- 0.39 h) when compared to fosfosal alone (1.55 +/- 0.35 h). Regarding codeine compared in combination with fosfosal, no significant differences were observed in Cmax and AUC values, while tmax showed a higher value for the combination (1.75 +/- 0.6 vs 0.85 +/- 0.32 h). Although statistical differences in the elimination constant rate and MRT were found between both codeine administrations, these cannot be considered significant in clinical terms. The changes in bioavailability rate observed for both drugs when administered together provide support for the use of this combination in a single formulation.

Adult↗

PubMed1986

Treatment of mild to moderate pain of acute soft tissue injury: diflunisal vs acetaminophen with codeine.

Acute soft tissue injuries create pain and limitation of function. Treatment requires analgesia and time for full recovery. Acetaminophen with codeine (650 mg plus 60 mg, respectively, every 4 to 6 hours) is used frequently as the analgesic of choice. Diflunisal (1,000 mg initially then 500 mg twice a day) vs acetaminophen with codeine was prospectively studied in the treatment of acute mild to moderate pain from soft tissue injuries. Thirty-five patients with acute strains, sprains, or low back pain were randomized to treatment (17 acetaminophen with codeine vs 18 diflunisal). Both groups were similar in the amount of pain and type of injury at initiation of therapy. Patient pain rating went from 3.3 +/- 0.6 to 1.6 +/- 1.5 for acetaminophen with codeine and from 3.3 +/- 0.6 to 1.3 +/- 1.1 for diflunisal. However, 65 percent of acetaminophen with codeine patients experienced side effects, with 35 percent of these patients stopping the medication because of intolerable side effects. In the diflunisal group, 28 percent of the patients experienced side effects and 5 percent had to stop the medication early. Diflunisal was found to be an effective analgesic in mild to moderate pain of acute soft tissue injuries, and caused fewer and more tolerable side effects than did acetaminophen with codeine.

Acetaminophen↗

PubMed1987

Fiorinal with Codeine in the management of tension headache: impact of placebo response.

The well-known difficulty in distinguishing the response to a combination headache medication and its individual components in the presence of a high placebo response was again demonstrated in a randomized, double-blind, placebo-controlled, multi-center trial comparing Fiorinal with Codeine and its Fiorinal and codeine phosphate components in relieving the pain, tension, and muscle contraction associated with tension headache. In the original analysis of the study data, no distinction was apparent between patient response to Fiorinal with Codeine and the response to the individual components, a finding that appeared to conflict with the results of a similar earlier study. This apparent discrepancy was attributable to a high placebo response in the later study. Separation of study subjects according to their baseline level of anxiety and pain identified a subset of less anxious patients with mild to moderate pain severity who were least likely to respond to placebo. Analysis of data from these patients showed that Fiorinal with Codeine was significantly better than placebo in improving patients' self-ratings of various symptoms of tension headache at 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. The combination drug was also consistently superior to Fiorinal alone and codeine alone in improving the patients' self-evaluation items, and differences between the combination and its components were generally of statistical or borderline significance during the last half of the study. The investigators' assessments of the effect of treatment on the three principal variables in tension headache (namely, headache pain, psychic tension, and muscle contraction of the head, neck, and shoulders) at the final patient visit also showed Fiorinal with Codeine to be not only significantly superior to placebo but also consistently superior to either component. The superiority of the combination over Fiorinal alone achieved borderline significance for headache pain and psychic tension.

Adult↗

PubMed1986

Pentazocine and codeine: effects on human performance and mood and interactions with diazepam.

Effects of two opioid analgesics on performance and their interactions with diazepam were studied double-blind and cross over in ten healthy students. At two-week intervals the subjects received first a single oral dose of placebo, codeine (100 mg) or pentazocine (75 mg). Then, 1 h 30 min later they were all given diazepam (0.25 mg/kg) orally. Lastly, naloxone (0.4 mg) was injected intravenously at 4 h. In addition to this, the subjects on pentazocine received a second 75 mg dose at 3 h. Codeine and pentazocine alone failed to affect performance in objective tests (body sway, digit symbol substitution, flicker fusion, Maddox wing, nystagmus) recorded at 1 h 30 min. Visual analogue scales showed subjective drug effects: pentazocine made the volunteers talkative, contented, interested and energetic, whilst codeine rendered them mentally slow. 75 mg of pentazocine and 100 mg of codeine produced comparable plasma opiate activity (determined in morphine equivalents) according to radioreceptor bioassay with [3H]-dihydromorphine as a ligand. Impaired performance was clear at the tests done 1.5 and 2.5 h after diazepam. No major interactions were found between opiates and diazepam in objective tests with the exception that nystagmus was stronger after the combined treatment than after diazepam alone. Codeine reduced the absorption of diazepam. Subjectively codeine and pentazocine counteracted the effects of diazepam. The subjects overestimated their performance after opiate + diazepam when compared to diazepam alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1983

The peripheral analgesic effect of morphine, codeine, pentazocine and d-propoxyphene.

The prostaglandin hyperalgesia and tail immersion tests were used to evaluate the analgesic action of morphine, codeine, d-propoxyphene and pentazocine following intraperitoneal, intraplantar and intracerebroventricular administration to rats. In the prostaglandin hyperalgesia test, all drugs produced a dose-dependent analgesia by the various routes. The rank order of potency after intraperitoneal administration was morphine (100) greater than d-propoxyphene (4) greater than pentazocine (2) greater than codeine (1). Although morphine (ID50 = 4 micrograms) was a very potent analgesic when given intracerebroventricularly, very shallow dose-response curves were obtained with the other substances which promoted less than 30% of inhibition at doses up to 250 micrograms. In the paw, morphine (ID50 = 5 micrograms) was only 5-8 times more potent than pentazocine, propoxyphene and codeine. Thus, in contrast with morphine, intraplantar administration of codeine, pentazocine and d-propoxyphene is much more effective than intracerebroventricular administration. In the tail immersion test the smallest intraperitoneal doses which affected the reaction time were 9 mg/kg morphine, 16.2 mg/kg codeine and pentazocine and 48.6 mg/kg d-propoxyphene. When injected intracerebroventricularly morphine (10 micrograms) was the only opiate that caused a detectable analgesic effect. In the prostaglandin hyperalgesia test, a small dose of naloxone (1 micrograms) given into the rat paw significantly antagonized the analgesic effect of d-propoxyphene, codeine and pentazocine administered either intraperitoneally or intraplantarly. These results clearly indicate that a method involving or mimicking inflammatory hyperalgesia is much more sensitive in detecting opiate analgesia than a method which uses heat as a nociceptive stimulus. Furthermore, our results support the proposition that part of the overall analgesia which follows the systemic administration of opiates is due to a peripheral antinociceptive action.

Analgesia↗

PubMed1981

[Codeine seeking behavior in rats using a weight-pulling method].

The purpose of this work was to examine the development of preference for codeine and codeine-seeking behavior by using an apparatus in which rats were compelled to pull against a weight to gain access to codeine-admixed food but not in the case of normal food. Rats developed a strong preference for codeine-admixed food by the repetition of choice and forced trails. The preference for codeine-admixed food was maintained at levels between 60 to 80% for 14 days without any forced trial. After rats developed this preference, they were tested as to whether they might pull against the weight in the apparatus. We observed that the rats did pull at most 40-120 g/100 g body weight in order to reach the drug-admixed food. This is defined as maximum pulling weight. As the weight load was increased, the rats showed more frequent weight pulling behavior for the codeine-admixed food while the duration of eating decreased. The maximum weight pulled was more than 70 g/100 g body weight in 4 out of 6 rats. These results suggest that the degree of drug-seeking behavior in rats can be detected by the use of the weight-pulling method.

Animals↗

PubMed1982

Liquid chromatography of codeine in plasma with fluorescence detection.

This analytical method for easier determination of codeine in human plasma is based on "high-performance" liquid chromatography for separation and the natural fluorescence of codeine for detection. Codeine is extracted from alkalinized plasma with a mixture of hexane and dichloromethane, and the extract is further purified and chromatographed. The method can be used for routine assay of codeine at the concentrations of 10 micrograms/L or greater in human plasma. As little as 4 micrograms/L can be detected. Coefficients of variation for the assay of codeine in the concentration range of 10 to 100 micrograms/L were 2.2-7.4% (n = 6). We used this method to establish a concentration/time profile for plasma from a human volunteer after a 60-mg oral dose of codeine sulfate.

Administration, Oral↗

PubMed1993

Conjunctival provocation tests with codeine phosphate. Effect of disodium cromoglycate.

The reactivity of ocular mast cells is poorly characterized in man. Provocation tests with codeine phosphate, a molecule known to activate connective tissue mast cells, were performed in ten normal subjects. Ten-fold increasing concentrations of codeine phosphate (10(-5) to 10(-1) mg/mL) were tested in both eyes until a positive challenge was observed. Schirmer strips were placed under the eyelid and left for five minutes. A negative control was performed ten days later. All subjects had a strongly positive reaction for the same codeine phosphate concentration (10(-1) mg/mL). Histamine was released in 8/10 subjects (control: 7.06 +/- 4.19 nM/L, codeine phosphate: 18.2 +/- 15.7 nM/L, P < .018), PGD2 was released in 8/10 subjects (control: 0 codeine phosphate: 273.3 +/- 408.9 ng/L). Disodium cromoglycate blocked the release of histamine and PGD2. Codeine phosphate is potent at causing mast cell activation in the eye and this effect is blocked by disodium cromoglycate.

Adult↗

PubMed1993

Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis.

A 33-year-old Chinese woman with exercise-induced anaphylaxis after ingesting Chinese seafood noodle soup, was studied for skin test reactivity to food, histamine, and codeine. Prick skin tests were negative for shrimp, wheat, and chicken soup base, but were positive at 5 to 6 mm (wheal diameter) to the whole broth after it had been combined with the other ingredients. No significant (> 3 mm) wheals were observed in eight controls who were simultaneously tested with the broth. To assess the role of exercise, three series of skin tests were performed with histamine, codeine, and whole broth before and after aerobic exercise on two occasions. Codeine elicited consistent increases in wheal size after exercise compared with pre-exercise skin tests. Histamine and whole broth wheal sizes did not increase significantly. Three control subjects also had codeine and histamine skin tests before and after exercise, No exercise-associated increases were noted for codeine. Potential insights into mast cell abnormalities in exercise-induced anaphylaxis may be gained by skin testing patterns with codeine and other mast cell degranulating agents.

Adult↗

PubMed1993

Codeine disposition in sickle cell patients compared with healthy volunteers.

The pharmacokinetics of codeine were determined after oral administration of codeine sulfate (60 mg) with sickle cell patients (SCPs) and healthy controls (HCs). Plasma concentrations of codeine were measured by reversed-phase high-pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated using both compartmental and noncompartmental analysis. No significant differences were observed in time to reach maximum peak plasma concentration (tmax) (1.0 +/- 0.4 versus 1.4 +/- 1.0 hours), maximum peak plasma concentration (Cmax) (172 +/- 25 versus 225 +/- 97 ng/mL), area under the curve (AUC infinity) (590 +/- 96 versus 779 +/- 234 ng*h/mL), and Cl/F (104 +/- 17 versus 89 +/- 27 L/h) between SCPs and HCs. Conversely, significant differences were observed in mean residence time (MRT) (3.7 +/- 0.3 versus 4.7 +/- 0.3 hours) and half-life (t1/2) (1.7 +/- 0.2 versus 2.8 +/- 0.3 hours). In a separate study, significant differences were observed in the in vitro plasma protein binding of codeine in SCPs (66.0 +/- 8.6%) and HCs (30.5 +/- 2.7%) as well as in vivo binding (68.4 +/- 11.1% for SCPs versus 29.2 +/- 3.4% for HCs). Codeine is a relatively high-extraction drug that is primarily eliminated by metabolism in the liver. Generally, the clearance of such drugs is approximately equal to hepatic blood flow and is not affected by changes in protein binding. Therefore, the change in t1/2 observed in SCPs can be attributed to changes in volume of distribution rather than clearance.

Adult↗

PubMed1980

High-performance liquid chromatographic analysis of codeine in syrups using ion-pair formation.

The chromatographic behavior of morphine, codeine, and ethylmorphine was examined using reversed-phase high-performance liquid chromatography and ion-pair formation. Alkyl sulfonates and sulfates significantly increased the retention times for these compounds. The carbon chain length of the pairing ions was linearly related to the log of the capacity factors of these amine drugs. A mechanism for the increased retention based on ion-pair formation in the mobile phase is proposed. The use of dioctyl sodium sulfosuccinate as a pairing ion for codeine is described, and a method utilizing this pairing ion was developed for the quantitation of codeine in syrups. This method was applied successfully to various syrups containing codeine or codeine phosphate.

Chromatography, High Pressure Liquid↗

PubMed1984

Determination of codeine in human plasma by reverse-phase high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the determination of codeine in human plasma is described. The specific, precise, and sensitive method can be used to determine plasma codeine levels after administration of therapeutic doses of codeine. After purification on a C18 extraction column, codeine in the form of hydrochloride is eluted. After addition of the internal standard, the codeine is separated on a reverse-phase C18 column using a slightly alkaline mobile phase and is then determined by UV detection. The analysis takes 3.5 min per run; the limit of detection is approximately 3 micrograms/L for a 50-microL loop and 800 microL of plasma. The absolute recovery is 98.4 +/- 6.7% (n = 14) in the 10-300-micrograms/L range. Within the range, the calibration curve is linear.

Adult↗