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Measurement of meperidine and normeperidine in human breast milk by selected ion monitoring.

A technique is described for extraction and quantitation of meperidine and normeperidine from breast milk by gas chromatography/mass spectrometry. Both compounds were measured in breast milk from parturients who received the drug for postpartum pain relief. The technique is sensitive to 1 ng ml-1 and standard curves were linear at 1.5-2000 ng ml-1. Levels in breast milk samples were 36.2-314 ng ml-1 and 0-333 ng ml-1 for meperidine and normeperidine, respectively. Preliminary results suggest that postpartum pain medication with meperidine results in considerable levels of both meperidine and its active metabolite, normeperidine, in breast milk.

Female↗

Gastric and biliary excretion of meperidine in man.

The role and importance of enterogastric secretion in the disposition and elimination of the weak base, meperidine (pKa 8.63), was studied after intravenous administration (50 mg) of the drug to 6 normal volunteers. Continuous collection of the gastric fluid over a 4-hr period demonstrated the establishment of high gastric fluid/plasma concentration ratios for meperidine (mean about 50, range, 10 to 200). However, the total amount of drug recovered, even after correction for incomplete collection, was only a small percentage of the administered dose. Under basal conditions a mean +/- SE of 1.9 +/- 0.3 mg, equivalent to 3.7% of the administered dose, was found in the total gastric aspirate. Stimulation of gastric secretion by subcutaneous injection of betazole (1.5 mg/kg) increased this recovery to 3.6 +/- 0.3 mg (7.2%) primarily due to the increase in gastric volumen output. Aspiration of the gastric fluid in either the basal or stimulated situation had no observable effect upon the plasma concentration/time profile of meperidine whether assessed by the terminal half-life, t 1/2 beta, or the plasma clearance; control values were 3.8 +/- hr and 1,190 +/- 130 ml/min, respectively. In 2 subjects "bile fluid" was also collected for 2.5 hr and found to contain less than 0.2% of the administered dose. Enterosystemic recycling is therefore of minor importance in the disposition and elimination of meperidine in man.

Adult↗

Diazepam and meperidine on arterial blood gases in patients with chronic obstructive pulmonary disease.

Arterial blood gases were not significantly altered by 0.15 mg/kg intravenous dose of diazepam in patients with chronic obstructive lung disease. The PalphaO-2 was significantly reduced and the P-alphaCO-2 increased after administration of 1.5 mg/kg meperidine intravenously and the combination of 1.5 mg/kg meperidine with 0.15 mg/kg diazepam. Diazepam did not, however, significantly increase the ventilatory depression induced by meperidine. Therefore, 0.15 mg/kg diazepam intravenously causes no ventilatory depression by meperidine in patients with chronic obstructive lung diseases.

Adult↗

Effect of hydroxyzine and meperidine on arterial blood gases in healthy human volunteers.

Because hydroxyzine hydrochloride is frequently used to tranquilize patients, who are receiving narcotic analgesics for pain relief, its effect alone and in combination with meperidine on arterial blood gases and ventilation in patients at rest was evaluated in 65 healthy volunteers, who gave informed consent. Hydroxyzine hydrochloride, 1.5 mg/kg IV given over 30 seconds, caused no decrease but rather a significant (P less than .001) increase in PaO2 and no increase in PaCO2 and/or pH at 5, 10, 20, 30, and 60 minutes (N = 29; mean age = 47.0 years). Meperidine, 1.5 mg/kg IV given over 30 seconds, caused a significant (P less than .01) reduction in PaO2 at 5 minutes indicating ventilatory depression but no increase in PaCO2 and/or pH (N = 19; mean age = 32.4 years). The combination of the same doses of hydroxyzine with meperidine IV caused a significantly greater decrease in PaO2 only at 10 minutes but a greater increase in PaCO2 and pH at all times for 60 minutes than did meperidine alone (N = 17; mean age = 39.5 years), which indicates greater ventilatory depression with the combination than with hydroxyzine alone. However, PaO2, PaCO2 and pH remained within the awake normal ranges for PaO2, PaCO2, and pH for the age group of volunteers even at 10 minutes after IV injection of the drug combination when most of the volunteers were asleep. In conclusion, hydroxyzine even when given IV in excess of the maximum IM therapeutic doses caused no changes in PaO2, PaCO2 or pH, which would indicate clinically important ventilatory depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Micromethod for determination of meperidine in plasma.

A GLC method utilizing a flame-ionization detector is described for the analysis of meperidine in blood plasma. Meperidine is extracted with ether from plasma that has been made basic with sodium hydroxide. The ether extract is evaporated to dryness, and the residue is dissolved in carbon disulfide for GLC analysis. An internal standard, N',N'-diethylaminoacetyl-2,6-xylidine, is used to quantitate meperidine. The extraction efficiency from plasma is 85%, and as little as 0.05 microng of meperidine can be quantitatively determined in 1 ml of plasma.

Chromatography, Gas↗

Impurities in drugs II: meperidine and its formulations.

Three lots of meperidine hydrochloride, seven lots of meperidine tablets, and 41 lots of meperidine injectables were examined for impurities by TLC. Impurities found were ethyl 1-benzyl-4-phenyl-4-piperidinecarboxylate, methyl-4-piperidinecarboxylate, ethyl-4-phenyl-4-piperidinecarboxylate, and three unidentified compounds. Not all impurities were found in every lot of drug investigated, and none of the impurities exceeded a concentration of 1% of the meperidine present.

Chromatography, Thin Layer↗

Uptake and elution of chlormethiazole, meperidine, and minaxolone in the hindquarters of sheep: implications for clearance calculations.

Mass balance principles were used to describe the uptake and elution of chlormethiazole, meperidine, and minaxolone in the hindquarters of sheep. Sheep received a right atrial infusion of either chlormethiazole (3.71 mg/min) or meperidine (2.70 mg/min) for 180 min, or minaxolone (0.37 mg/min) for 120 min. Paired arterial and inferior vena cava (draining the hindquarters) blood samples were taken during and after the infusion. The mean and SD (n = 4) of the time-averaged extraction ratios across the hindquarters (determined from the relevant arterio-venous area under blood concentration--time curves) were 0.12 (0.10), 0.36 (0.13), and 0.27 (0.05) for chlormethiazole, meperidine, and minaxolone, respectively. The rank order of the rate of uptake of the drugs into the hindquarters was the same as the rank order of their lipophilicity, and uptake still continued when both the arterial and inferior vena cava drug concentrations were essentially constant. For chlormethiazole, meperidine, and minaxolone, 48% (44), 4% (6), and 35% (17), respectively, of the drug taken into the hindquarters eluted from the hindquarters after the infusion. Drug uptake and retention in extravisceral tissues, represented here by the hindquarters, can result in the mean total body drug clearance being overestimated when determined by traditional systemic pharmacokinetic methods.

Anesthetics↗

Effects of meperidine on operant behavioral thermoregulation in mice under conditions of symmetrical thermal drive.

The effects of meperidine on operant behavioral thermoregulation were investigated using a convective thermal controller and mice trained to alternate at will the thermal-drive condition, changing it from an air flow of 15 degrees C to one of 45 degrees C, and vice versa. Administration of 15 mg/kg meperidine resulted in significantly lower response rates, a significantly larger fraction of time spent in one (mostly cold) drive condition, and significantly lower body temperatures than administration of saline. In a second experiment the animal was automatically returned to the hot-drive condition every 3 min unless it had been exposed to this condition in the previous 0.4 min although otherwise it remained free to alternative drive conditions at will. Under these conditions, meperidine-treated animals also spent significantly more time in cold drive and had significantly lower body temperatures than control animals, in spite of lower response rates. Pretreatment with 4.5 mg/kg tranylcypromine (4 h prior) did not significantly alter the effects of meperidine administration in either experiment.

Animals↗

Meperidine surveillance in an outpatient department: the recognition of misuse and its control.

The identification of two patients who were misusing meperidine prescribed in a hospital prompted the establishment of a surveillance system to examine the possible extent of the problem of prescription narcotic abuse. All outpatient prescriptions for meperidine in a six-month period were reviewed and 17 high users were identified who were considered to be at greatest risk of misuse; they received 55% of all meperidine dispensed from the OPD pharmacy. These persons obtained their prescriptions primarily through the emergency room, they rarely saw the same physician twice, and 12 of them carried a diagnosis of sickle cell disease. Among these patients, four cases of definite abuse were identified. Interventions aimed at promoting continuity of care to the high users led to a 66% reduction in meperidine prescribed to this group in the emergency room and to a shift in their care to the clinics. Establishment of a registry for narcotic surveillance is a first toward recognition of outpatient drug abuse. Limiting prescribing privileges to the physician responsible for a patient's long-term care can further decrease this risk.

Drug and Narcotic Control↗

Patient-controlled epidural analgesia after caesarean section using meperidine.

PURPOSE: To determine the effects of the addition of a background infusion to patient-controlled epidural analgesia (PCEA) using meperidine for analgesia after Caesarean section. METHODS: In a randomized, double-blind study, we assigned 40 patients having elective Caesarean section to receive postoperative analgesia by patient-controlled epidural analgesia (PCEA) using meperidine 5 mg.ml-1 with (group Pi) or without (group Po) a background infusion of 10 mg.hr-l. The PCEA settings (20 mg bolus, 10 min lockout interval, four-hour maximum dose 150 mg) were otherwise identical. We compared pain at rest, pain on coughing, side effects, number of PCEA demands, drug consumption and patient satisfaction between groups in the first 24 hr after surgery. RESULTS: Total consumption of meperidine was greater in group Pi (median 390 mg) than in group Po (median 240 mg; P = 0.017) and the number of PCEA demands was greater in group Po (median 12) than in group Pi (median 7.5; P = 0.012). Analgesia, side effects and patient satisfaction was similar between groups. CONCLUSION: Addition of a background infusion to PCEA using meperidine after Caesarean section has no clinical benefit.

Adjuvants, Anesthesia↗

Comparison of the effects of meperidine and nalbuphine on intrapartum fetal heart rate tracings.

OBJECTIVE: To examine the effects of meperidine and nalbuphine on intrapartum fetal heart rate (FHR) tracings using computer analysis. METHODS: We studied 28 women with uncomplicated pregnancies in early labor at term with reactive FHR tracings. The women were randomized to receive either meperidine 50 mg or nalbuphine 10 mg intravenously on request. One-hour FHR recordings were obtained before and immediately after administration of the medications. RESULTS: There were no significant differences in the FHR characteristics of the two groups during the pre-treatment period. Nalbuphine significantly decreased the number of accelerations of 10 beats per minute (17 versus 4, P = .003) and 15 beats per minute (10 versus 1.5, P = .001), time spent in episodes of high variation (35.5 versus 10 minutes, P = .004), long-term variation (47 versus 29.8 milliseconds, P = .002), and short-term variation (8.4 versus 6.4 milliseconds, P = .03). Meperidine had no significant effect on any FHR characteristic. CONCLUSION: In the early intrapartum period of normal term pregnancies and at commonly used dosages, nalbuphine had a significant effect on FHR tracings, whereas meperidine had no effect, as determined by computer analysis.

Adolescent↗

Double-blind comparison of nalbuphine and meperidine in combination with diazepam for intravenous conscious sedation in oral surgery outpatients.

Nalbuphine and meperidine were compared as analgesic components of intravenous conscious sedation in a double-blind, prospective trial of 47 patients undergoing elective oral surgery. Subjects were evaluated for pain intensity, pain relief, anxiety, sedation, recall, and vital signs at systematic observation points intraoperatively and postoperatively. At the conclusion of surgery 83% of patients who had received nalbuphine and 86% of patients treated with meperidine indicated complete pain relief. One observed adverse reaction was attributed to meperidine and another to the sedative component diazepam. No statistically significant differences were observed between nalbuphine and meperidine treatments.

Adult↗

Comparison of morphine, meperidine, anileridine, and alphaprodine on schedule-controlled responding and analgesia.

The effects of morphine, meperidine, alphaprodine, and anileridine were studied alone and in the presence of 1 mg/kg of naloxone in rats on level pressing under a fixed-ratio 20-response schedule of food presentation and on tail-withdrawal latency from warm water (55 degrees C) as a measure of analgesia. All four narcotics decreased rates of lever pressing and increased tail-withdrawal latencies. Naloxone antagonized the effects of all four narcotics on tail-withdrawal, but did not antagonize the rate-decreasing effect of meperidine on lever pressing. Naloxone shifted the morphine dose-effect for lever-pressing by a factor of 4-8; the alphaprodine dose-effect curve by a factor of 4-8; and the anileridine dose-effect curve by a factor of 2. These results strengthen the interpretation that meperidine's effect on schedule-controlled responding is not mediated by a narcotic action whereas the analgesic effect is. The results also suggest that anileridine has significant non-narcotic actions like meperidine.

Alphaprodine↗

Time-dependent generalization of morphine stimulus properties to meperidine: antagonism by naloxone.

The time course of the stimulus generalization to morphine by meperidine (20 mg/kg) was determined in rats trained to discriminate morphine (10 mg/kg) from saline in a standard two-lever procedure with food reinforcement. It was found that morphine lever selection following meperidine was a strictly time-dependent phenomenon. Naloxone (0.3 mg/kg) antagonized the stimulus properties of both morphine and meperidine; however, the antagonism was significantly more pronounced against morphine. The results suggest that there may be certain differences in the neuropharmacology of the stimulus properties of morphine and meperidine.

Animals↗

Analysis of meperidine and normeperidine in serum and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the simultaneous analysis of meperidine and normeperidine in serum and urine. A 1-ml sample aliquot is extracted into hexane, then back-extracted into a small volume of dilute acid which is injected onto a cyanopropyl analytical column. Absorbance of the column effluent is monitored at 205 nm. Two internal standards are employed, diphenhydramine for meperidine and nordiphenhydramine for normeperidine. Chromatography of the four compounds takes 4 min. Serum concentration--time curves of meperidine and normeperidine are presented for eight healthy subjects following single 70-mg bolus injections of meperidine.

Adult↗

Pediatric patient-controlled analgesia with morphine versus meperidine.

To assess prospectively any difference in either analgesia or side effect frequency with morphine versus meperidine, 50 patients, ages 8-16 years, were randomly assigned to receive postoperative patient-controlled analgesia (PCA) with either morphine or meperidine. A numerical rating scale pain score was obtained from each patient twice a day, and any nausea, vomiting, pruritus, or urinary retention requiring catheterization was noted. No significant difference in the incidence of side effects was noted between the morphine and meperidine groups; however, pain scores during morphine PCA were significantly less than those during meperidine PCA (P less than 0.001). These results suggest that morphine is the better opioid for pediatric PCA.

Adolescent↗

Acute neurotoxicity of meperidine in an infant.

We report a 6-week-old boy with meperidine neurotoxicity. What distinguished our patient from those previously reported was his minimal exposure to therapeutic doses of meperidine in the setting of normal renal function, and no history of sickle cell anemia, cancer, hepatitis, or cirrhosis. In addition, our patient had no abnormal changes in the electroencephalogram during the event. After only 2 doses of meperidine, he exhibited acute orofacial dyskinesias consisting of tongue thrusting, lip pursing, and facial grimacing combined with prominent flexion of the arms and stiffening of his legs. However, a normal sucking response remained. His symptoms resolved over the next 36 hours and did not respond to naloxone. We believe that this unique presentation of meperidine-induced neurotoxicity may be due to changes in the basal ganglia resulting from perinatal hypoxemia.

Analgesics, Opioid↗

Structure-activity studies of 3'-4'-dichloro-meperidine analogues at dopamine and serotonin transporters.

The structure-activity relationships of 3',4'-dichloro-meperidine were investigated at dopamine (DAT) and serotonin transporters (SERT). Large ester substituents and lipophilic groups at the 4-position favored molecular recognition at the SERT. The benzyl ester of 3',4'-dichloro-meperidine exhibited high potency and high selectivity for the SERT (DAT/SERT=760). Chemical modification of the ester group and N-substitution generally led to compounds with decreased DAT affinity. Only small esters and alkyl groups were tolerated at the 4-position of the meperidine ring system by the DAT. Overall, the meperidine analogues were generally more selective for the SERT than for the DAT.

Binding, Competitive↗