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PubMed1980

Narcotic-reinforced responding: a rapid evaluation procedure.

Rhesus monkeys were conditioned to lever press for intravenous injections of codeine. The self-injection behavior was brought under the control of a schedule of drug delivery and access to the codeine schedule was made available twice each day. Subsequently, a variety of doses of codeine and saline were compared to the dose used to condition and maintain self-injection responding. Each change in drug condition was maintained for only a single experimental session. The procedure is recommended for rapid evaluation of drugs for their capacity to reinforce self-injection behavior.

Animals↗
PubMed1987

Transcutaneous electrical nerve stimulation versus oral analgesic: a randomized double-blind controlled study in acute traumatic pain.

A double-blind controlled analgesic study was undertaken in outpatients suffering acute traumatic pain. One hundred patients completed the study and were randomly assigned to four treatment groups, each receiving either functioning transcutaneous electrical nerve stimulators (TENS), placebo TENS, acetaminophen with codeine and a functioning TENS, or acetaminophen with codeine and a placebo TENS. Pain was assessed prior to treatment, at 48 hours, and at one month using a visual analog scale. A statistically significant difference in pain relief occurred between the placebo and functioning TENS groups. The TENS was approximately as effective as acetaminophen (300-600 mg) with codeine (30-60 mg) but had no side effects. Transcutaneous electrical nerve stimulators have been shown to be effective in the management of acute traumatic pain and may be indicated for patients who cannot be given medications.

Acetaminophen↗
PubMed2004

Drug interactions with the potential to prevent prodrug activation as a common source of irrational prescribing in hospital inpatients.

OBJECTIVE: Our objective was to investigate the frequency of potential drug-drug interactions between the prodrugs losartan, codeine, and tramadol and drugs known to inhibit their activation in hospitalized patients. METHODS: The frequency of coadministration between losartan and well-established cytochrome P450 (CYP) 2C9 inhibitors, as well as codeine and tramadol and CYP2D6 inhibitors, was studied by use of data from a university hospital medication database. The study population comprised all patients treated in internal medicine, pulmonary medicine, oncology, and neurology wards (105,533 treatment periods and 65,526 patients) between July 1, 1996, and June 30, 2002 (6 years). RESULTS: Every fifth patient receiving losartan, codeine, or tramadol was concomitantly taking another drug that has the potential to inhibit the activation of these drugs. During the 6-year time period, 1999 patients were exposed to a potential interaction. Interactions occurred more commonly in internal medicine wards (odds ratio, 2.3; 95% confidence interval, 2.1-2.5) and in women (odds ratio, 1.5; 95% confidence interval, 1.4-1.7). CONCLUSIONS: Coadministration of drugs that potentially result in inhibition of prodrug activation present a common and unrecognized source of irrational prescribing.

Adolescent↗
PubMed2006

The effect of montelukast (10mg daily) and loratadine (10mg daily) on wheal, flare and itching reactions in skin prick tests.

UNLABELLED: Antileukotriene agents are widely used for the treatment of allergic conditions including bronchial asthma and allergic rhinitis. The influence of montelukast on skin reactivity has not been clearly evaluated. The aim of this study was to determine the effect of montelukast on wheal, flare and itching in skin prick tests (SPTs). METHODS: Fifteen atopic patients (5 women and 10 men) with average age 28.04 (SD+/-8.24) were tested with histamine, codeine, negative control solution and allergen extract (grasses). Montelukast (10mg), loratadine (10mg) or placebo were given to the volunteers for 5 days in a double-blind manner, followed by SPT, with 14 days of wash-out period. RESULTS: There was no differences in wheal, flare and itching (p=0.205; 0.086 and 0.069, respectively, Wilcoxon rank-sum test) between SPT performed after placebo and wash-out period. The analysis revealed a statistically significant suppression of wheal and flare by loratadine (p<0.05 for all tested solutions). Pre-treatment with montelukast did not influence wheal size (p=0.099, 0.21, 0.066 for histamine, codeine and allergens, respectively), but significantly reduced flare (p=0.005; 0.003; 0.02 for histamine, codeine and allergens, respectively). We found a significant suppression of itching produced by montelukast (p=0.02) and loratadine (p=0.03) as compared to placebo (p=0.068 vs. wash out). CONCLUSIONS: Our data show a tendency to suppressive effect of montelukast on flare and itching but not on wheal which is basic for SPT interpretation. We conclude that found suppression have little impact on clinical effectiveness of SPT as a diagnostic tool.

Acetates↗
PubMed2001

Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator-controlled clinical trial.

BACKGROUND: In recent studies of acute pain and primary dysmenorrhea, rofecoxib, a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-2 enzyme, was found to be similar in efficacy to ibuprofen and naproxen sodium. OBJECTIVE: The purpose of this study was to determine the analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain. METHODS: In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate or severe pain after the surgical extraction of > or = 2 third molars, at least 1 of which was a mandibular impaction, were randomized to receive placebo, rofecoxib 50 mg, or codeine 60 mg/acetaminophen 600 mg. Patient evaluations of pain intensity, pain relief, and global assessments were recorded throughout the 24-hour period after dosing. The 2-stopwatch method was used to determine time to confirmed perceptible pain relief. The primary end point assessing overall analgesic effect was total pain relief over 6 hours (TOPAR6). Secondary end points were patient global assessment of response to therapy (PGART) at 6 hours, onset of analgesia, peak analgesic effect, and duration of analgesia. RESULTS: A total of 393 patients were enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31 received placebo. The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 (12.4 vs 7.0; P < 0.001) and PGART at 6 hours (P < 0.001). The onset of analgesic effect was similar for rofecoxib and codeine/acetaminophen. Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen group (P < 0.001), as was the duration of analgesic effect measured by the time to rescue analgesia (9.6 hours vs 2.3 hours, P < 0.001). Adverse events were reported in 33.0%, 46.1%, and 32.3% of patients treated with rofecoxib, codeine/acetaminophen, and placebo, respectively. The most common adverse events were nausea (6.0%, 25.0%, and 9.7%, respectively) and vomiting (3.8%, 18.3%, and 6.5%, respectively). Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall (P < 0.050) and nausea in particular (P < 0.001). CONCLUSION: In this study of moderate to severe postoperative dental pain, the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen, with a lower incidence of adverse events and nausea.

Acetaminophen↗
PubMed2002

The effect of ketoprofen on recovery after tonsillectomy in children: a 3-week follow-up study.

OBJECTIVE: To evaluate recovery after tonsillectomy in children, and to determine the safety and efficacy of ketoprofen in pain treatment after discharge. STUDY DESIGN: A prospective, longitudinal study in 102 children undergoing tonsillectomy. METHODS: All children underwent tonsillectomy under a same general anesthesia. At discharge, all patients were prescribed ketoprofen capsules at a dose of 3-5 mg(-1) kg(-1) per 24 h for postoperative pain control at home, with paracetamol or paracetamol-codeine tablets for rescue analgesia. At home, the patients recorded pain and analgesic consumption each day for the first week after surgery. At 3 weeks, patients recorded the total analgesic requirement, duration of pain, and all adverse events during recovery and return to normal daily activities. RESULTS: The median of pain cessation was 9 days (range 1-20 days) and the median duration of analgesic treatment was 10 days (4-19 days). More than 50% of the patients needed rescue analgesic daily during the first week after tonsillectomy. Ketoprofen combined with paracetamol or paracetamol-codeine provided sufficient analgesia for most children. However, the analgesic action of drugs was too short to achieve pain relief, which allow undisturbed sleep during the first postoperative nights. A return back to normal daily activities took place after 9 days (2-26 days). The influence of age for pain pattern was negligible. Five patients needed electrocautery to stop postoperative bleeding. No other serious adverse-events occurred. CONCLUSIONS: The main problem after tonsillectomy is significant pain that may last 9 days or longer after surgery. Ketoprofen combined with paracetamol-codeine seems to provide a sufficient analgesia, but before ketoprofen may be recommended for children during tonsillectomy a larger study is needed to show whether or not ketoprofen increases the hemorrhage rate.

Acetaminophen↗
PubMed2003

High prevalence of 6-acetylmorphine in morphine-positive oral fluid specimens.

Identification of 6-acetylmorphine, a specific metabolite of heroin, is considered to be definitive evidence of heroin use. Although 6-acetylmorphine has been identified in oral fluid following controlled heroin administration, no prevalence data is available for oral fluid specimens collected in the workplace. We evaluated the prevalence of positive test results for 6-acetylmorphine in 77,218 oral fluid specimens collected over a 10-month period (January-October 2001) from private workplace testing programs. Specimens were analyzed by Intercept immunoassay (cutoff concentration=30 ng/ml) and confirmed by GC-MS-MS (cutoff concentrations=30 ng/ml for morphine and codeine, and 3 ng/ml for 6-acetylmorphine). Only morphine-positive oral fluid specimens were tested by GC-MS-MS for 6-acetylmorphine. A total of 48 confirmed positive morphine results were identified. An additional 107 specimens were confirmed for codeine only. Of the 48 morphine-positive specimens, 32 (66.7%) specimens were positive for 6-acetylmorphine. Mean concentrations (+/-S.E.M.) of morphine, 6-acetylmorphine and codeine in the 32 specimens were 755+/-201, 416+/-168 and 196+/-36 ng/ml, respectively. Concentrations of 6-acetylmorphine in oral fluid ranged from 3 to 4095 ng/ml. The mean ratio (+/-S.E.M.) of 6-acetylmorphine/morphine was 0.33+/-0.06. It is suggested that, based on controlled dose studies of heroin administration, ratios >1 of 6-acetylmorphine/morphine in oral fluid are consistent with heroin use within the last hour before specimen collection. The confirmation of 6-acetylmorphine in 66.7% of morphine-positive oral fluid specimens indicates that oral fluid testing for opioids may offer advantages over urine in workplace drug testing programs and in testing drugged drivers for recent heroin use.

Codeine↗
PubMed2000

HPLC determination of guaifenesin with selected medications on underivatized silica with an aqueous-organic mobile phase.

A high performance liquid chromatography procedure has been developed for the simultaneous determination of guaifenesin pseudoephedrine-dextromethorphan and guaifenesin-pseudoephedrine in commercially available capsule dosage forms and guaifenesin-codeine in a commercial cough syrup dosage form. The separation and quantitation are achieved on a 25-cm underivatized silica column using a mobile phase of 60:40%) v/v 6.25 mM phosphate buffer, pH 3.0 - acetonitrile at a flow rate of 1 ml min(-1) with detection of all analytes at 216 nm. The separation is achieved within 10 min for each drug mixture. The method showed linearity for the guaifenesin-pseudoephedrine-dextromethorphan mixture in the 50-200, 7.5-30 and 2.5-10, microg ml(-1) ranges, respectively. The intra- and inter-day RSDs ranged from 0.23 to 4.20%, 0.18 to 2.85%, and 0.13 to 5.04% for guaifenesin, pseudoephedrine, and dextromethorphan, respectively. The guaifenesin pseudoephedrine mixture yielded linear ranges of 25-100 and 3.75-15 microg ml(-1) and intra- and inter-day RSDs ranged from 0.65 to 4.18% and 0.23 to 3.00% for guaifenesin and pseudoephedrine, respectively. The method showed linearity for the guaifenesin-codeine mixture in the 25-100 and 2.5-10 microg ml(-1) ranges and RSDs ranged from 0.37 to 4.25% and 0.14 to 2.08% for guaifenesin and codeine, respectively.

Antitussive Agents↗
PubMed2002

[Postoperative comfort in pediatric outpatient tonsillectomy].

OBJECTIVE: Evaluate the comfort in children after ambulatory tonsillectomy, disregarding the surgical technique and with a systematic prescription of paracetamol and codeine. The study lasted 4 days including the day of surgery. STUDY DESIGN: [corrected] Prospective study during 5 months. PATIENTS AND METHODS: We performed a prospective study over a five-month period to evaluate the comfort in children after ambulatory tonsillectomy. Opioids were used for analgesia during surgery, morphine and propacetamol in the recovery room, and a systematic prescription of paracetamol-codeine between Day 0 to Day 3 at home. The assessment of pain was made by nurses and the family, considering 6 endpoints: spontaneous pain and when swallowing by verbal scale (0 to 4), occurrence of PONV (0 or 1), quality of sleep (0 or 1), quality of feeding (0 or 1) and play (0 or 1), combined in a global score of 0 to 12, with a score < or = 4 very satisfactory. RESULTS: 78 children were included, 49 tonsillectomy by dissection, 29 by Sluder. The score were < or = 4 at Day 0 and Day 1 in 53 children, but statistical analysis (univariate analysis) showed difference between the two surgical procedures with a global comfort score better and PONV lower with dissection procedure. CONCLUSION: The use of paracetamol-codeine after tonsillectomy offers a reliable analgesia with very satisfactory scores of comfort. Such prescription is effective in ambulatory tonsillectomy if a rigorous selection of patients is made.

Acetaminophen↗
PubMedDate not supplied

The efficacy of ANSAID (flurbiprofen) as an analgesic in foot surgery.

Eighty-three patients scheduled for outpatient surgery were enrolled in this double-blind, randomized trial designed to compare the safety and efficacy of single and multiple doses of flurbiprofen 50 mg. and acetaminophen 300 mg. plus codeine phosphate 30 mg. During the multiple dose segment, statistically significant differences were observed during the first 24 hour postoperative period regarding relief of pain and pain intensity. Flurbiprofen provided greater relief of pain than the acetaminophen with codeine phosphate combination. This study supports the use of flurbiprofen as a suitable alternative to acetaminophen plus codeine phosphate in the treatment of postoperative pain following foot surgery.

Acetaminophen↗
PubMed1997

Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study.

1. Although it is well known that morphine induces significant immunosuppression, the potential immunosuppressive activity of morphine derived drugs commonly used in the treatment of pain (codeine, hydromorphone, oxycodone) has never been evaluated. 2. We evaluated in the mouse the effect of the natural opiates (morphine and codeine) and synthetic derivatives (hydromorphone, oxycodone, nalorphine, naloxone and naltrexone) on antinociceptive thresholds and immune parameters (splenocyte proliferation, Natural Killer (NK) cell activity and interleukin-2 (IL-2) production). 3. Morphine displayed a potent immunosuppressive effect that was not dose-related to the antinociceptive effect, codeine possessed a weak antinociceptive effect and limited immunosuppressive activity; nalorphine, a mu-antagonist and kappa-agonist, exerted a potent immunosuppressive effect, but had very weak antinociceptive activity. The pure kappa-antagonist nor-BNI antagonized the antinociceptive, but not the immunosuppressive effect of nalorphine. 4. Hydromorphone and oxycodone, potent antinociceptive drugs, were devoid of immunosuppressive effects. 5. The pure antagonists naloxone and naltrexone potentiated immune responses. 6. Our data indicate that the C6 carbonyl substitution, together with the presence of a C7-8 single bond potentiates the antinociceptive effect, but abolishes immunosuppression (hydromorphone and oxycodone). 7. The single substitution of an allyl on the piperidinic ring resulted in a molecule that antagonized the antinociceptive effect but maintained the immunosuppressive effect. 8. Molecules that carry modifications of C6, the C7-8 bond and C14, together with an allyl or caboxymethyl group on the piperidinic ring antagonized both the antinociceptive and the immunosuppressive effect of opiates and were themselves immunostimulants.

Animals↗
PubMed1998

Variation in surgical trauma and baseline pain intensity: effects on assay sensitivity of an analgesic trial.

The aims of this study were to test the hypotheses that the type of 3rd molar removal determines baseline pain and that baseline pain influences analgesic assay sensitivity. Three groups of patients were studied: (i) 100 patients that had one fully erupted maxillary 3rd molar extracted; (ii) 95 patients that had one lower impacted 3rd molar surgically removed; and (iii) 98 patients that had two ipsilateral impacted 3rd molars surgically removed. In a randomized, double-blind fashion, the patients received (every third hour, three times) either: (i) paracetamol 1g; (ii) paracetamol 1g plus codeine 60 mg; or (iii) placebo. Baseline pain intensity (100 mm Visual Analogue Scale) was significantly lower after extraction (8 mm (2-20)) (=median (25th -75th percentile) than after surgical removal of one 3rd molar (35 mm (15-57)), which was significantly lower than pain intensity after surgical removal of two 3rd molars (49 mm (24-82)). Analgesic effects of the active test drugs were superior to placebo. Paracetamol with and without codeine could be distinguished in patients after surgical removal of one 3rd molar. In conclusion, baseline pain was related to the degree of surgical trauma, but large inter-individual variation in baseline pain intensity reduced the ability to distinguish between paracetamol with and without codeine.

Acetaminophen↗
PubMed1999

Axillary brachial plexus block for perioperative analgesia in 250 children.

A cannula technique for axillary brachial plexus block in combination with general anaesthesia has been in use since 1994 for children undergoing surgical correction of congenital hand anomalies. During a 4-year period data were collected on 250 procedures in 185 patients of median age 3 years detailing the block technique and the intraoperative and postoperative analgesic requirements. Fifteen patients (6%) required supplemental intravenous opioid intraoperatively and this is taken as a marker of failure of the block. Ninety-five patients (38%) required postoperative codeine phosphate with a mean time to receiving codeine phosphate of 9 h. Postoperative pain was controlled in this series with oral analgesia in all but six patients who received parenteral codeine. It is proposed that a cannula technique is an effective and safe method of producing axillary brachial plexus block in children.

Anesthesia, General↗
PubMed1996

Pain after craniotomy. A time for reappraisal?

Pain and nausea were prospectively assessed in 52 patients following elective craniotomy. When assessed at 6-hourly intervals the mean pain scores in patients during the first 24 h for all types of craniotomy were relatively low. However, for a period of at least 2 h 18% of patients complained of excruciating pain, 37% of patients complained of severe pain, 29% of patients complained of moderate pain, 4% of patients complained of mild pain and only 12% of patients complained of no pain in the 24 h following craniotomy. The mean dose of codeine phosphate used within the study period was 123 mg (SD 81). No statistically significant differences in severity of pain or use of codeine phosphate were found when comparing patients undergoing craniotomy at different sites. For at least 2 h 37% of patients complained of severe nausea or vomiting, 35% of patients complained of moderate nausea and only 29% of patients reported no symptoms of nausea during the 24-h study period. Again, no statistically significant differences were found in the severity of emetic symptoms when comparing patients undergoing craniotomy at different sites. Contrary to standard assumptions, severe or moderate pain in the first 24 h after craniotomy is common and is poorly treated with codeine phosphate alone.

Adolescent↗
PubMed2006

Obviation of opioid withdrawal syndrome by concomitant administration of naltrexone in microgram doses: two psychonautic bioassays.

Two psychonautic bioassays (self-experiments) in stepwise and abrupt cessation of long-term daily oral ingestion habits of 800 mg of codeine phosphate are presented. Concomitant administration of minute doses (about 0.5 mcg) of the opioid antagonist naltrexone with each dose of codeine was found in both cases to obviate the expected opioid withdrawal syndrome, resulting in asymptomatic and uneventful transitions from physical opioid dependency states to exogenous opioid-free metabolism. These experiments are analyzed in the context of a conjectured, rapid, iterative reduction and complete elimination of opioid tolerance, once acquired. It was found that coadministration of naltrexone with codeine phosphate obviated the development of both tolerance and physical dependency over several months of four daily oral doses of 200 mg, allowing abrupt ("cold turkey"), asymptomatic and uneventful withdrawal. This points the way to the biochemical substrate of opioid tolerance itself, and shows that this can easily and inexpensively be blocked, even over months of iterative oral administration of substantial doses of opioid analgesics. Finally, it suggests the opioid withdrawal syndrome is directly related to the physiology of opioid tolerance, and can be prevented by blocking tolerance itself. Even when tolerance has been acquired, this can be reduced stepwise over a matter of days, with no symptoms of opioid withdrawal syndrome.

Codeine↗
PubMedDate not supplied

Preliminary evaluation of the Abbott TDx for benzoylecgonine and opiate screening in whole blood.

A method for the detection of benzoylecgonine (cocaine metabolite) and opiates in whole blood is described. This method employs the Abbott TDx fluorescence polarization immunoassay technique, which was designed for urine analysis. Drug-free whole blood was spiked with varying concentrations of benzoylecgonine, morphine, and codeine. Samples were prepared for analysis by adding 300 microL of 10% trichloroacetic acid to 300 microL of blood. Specimens were vortexed and centrifuged with 50 microL of supernatant required per assay. Precision studies of six replicate samples spiked with benzoylecgonine at 0.5 mg/L gave a within-run CV of 4.7% and a between-run CV of 4.7% with a detection limit of 0.1 mg/L. Within-run CVs for morphine at 0.5 mg/L and 0.1 mg/L were 1.7% and 7.9% respectively. The detection limits for morphine and codeine were 0.05 mg/L. Correlation coefficients for spiked whole blood calibration curves of benzoylecgonine, morphine, and codeine were 0.984, 0.999, and 0.997 respectively. This preliminary evaluation demonstrates a potential application of the TDx fluorescence polarization immunoassay technique to the analysis of drugs in whole blood.

Cocaine↗
PubMed1997

Qualitative detection of opiates in sweat by EIA and GC-MS.

Sweat was collected with the PharmChek sweat patch, and drugs were eluted from the collection pad of the patch. A solid-phase enzyme immunoassay (EIA) using microtiter plates was modified for the analysis of opiates in sweat. After opiate administration, sweat contains primarily parent opiate (heroin, codeine) and lipophilic metabolites (6-monoacetylmorphine [6-MAM]). The immunoassay was determined to have a cross-reactivity with codeine of 588%, with hydrocodone of 143%, with diacetylmorphine of 28%, and with 6-MAM of 30% relative to 100% for the morphine calibrators. The optimum cutoff concentration for this modified assay was determined by receiver operator characteristic analysis using 215 patches from 95 subjects to be 10 ng/mL morphine equivalents. At this cutoff concentration the assay had a diagnostic sensitivity of 86.9% and a diagnostic specificity of 92.8% versus gas chromatography-mass spectrometry (GC-MS), which was the reference method. The positive predictive value at a prevalence of 50% was 86%. The intra-assay precision at 10 ng/mL was 7.8%, and the interassay coefficient of variation (CV) was 39%. Analysis of spiked patches around the cutoff gave a percent positive threshold of approximately 50% between 10 and 15 ng/mL and a 95% confidence level for a positive result by the EIA between 20 and 25 ng/mL. Eighteen possible adulterants that could be injected into or under the patch were studied. Two (tile cleaner and detergent) can cause false-positive responses in the immunoassay. Two adulterants reduced response to spiked drug (Visine eye drops and Ben Gay ointment), which could cause a false-negative response. All results were confirmed by GC-MS. The clinical sensitivity and specificity for detecting drug use by analyzing sweat collected from human subjects following known doses of codeine (0, 30, and 60 mg orally) or heroin (20 mg intravenously) were 76 and 100%, respectively.

Calibration↗
PubMed1977

Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs.

The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was added to a casein-sucrose-soybean oil basal diet for rats or a stock diet with 2% soybean oil for guinea pigs. The effect of vitamin E and cholestyramine was also examined in some experiments. Cholesterol feeding increased the rate of lipid peroxidation in liver and aortic homogenate both in rats and guinea pigs when fed non-vitamin E supplemented basal diets. Vitamin E supplementation prevented the increase in the aorta, but not as completely in the liver in rats, while the reverse was true in guinea pigs. The effect of cholestyramine was dependent on the level of vitamin E in the diet. Cholesterol feeding decreased glutathione peroxidase activities in rats and guinea pigs. In guinea pigs, cholesterol feeding also markedly decreased liver microsomal NADPH-dependent lipid peroxidation, codein hydroxylation and cytochrome P-450 levels especially when fed non-vitamin E supplemented basal diets. In rats, cholesterol feeding reduced liver microsomal NADPH-dependent lipid peroxidation and in some cases, increased microsomal codeine hydroxylation activities, but had no effect on microsomal cytochrome P-450 levels. Vitamin E supplementation increased liver and serum cholesterol levels in guinea pigs, but had no such effect in rats. Results of this study indicate that cholesterol feeding can result in various metabolic alterations in rats and guinea pigs. The implication of these alterations in atherogenesis requires further investigations.

Animals↗