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Clinical Pharmacology and Therapeutics Nov 1976The role and importance of enterogastric secretion in the disposition and elimination of the weak base, meperidine (pKa 8.63), was studied after intravenous...
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.
Topics: Adult; Bile; Female; Gastric Juice; Gastric Mucosa; Half-Life; Humans; Kinetics; Male; Meperidine
PubMed: 975725
DOI: 10.1002/cpt1976205546 -
The Journal of Pharmacology and... May 1979The renal excretion of meperidine by the fetus was determined in five chronic, unanesthesized fetal lamb preparations. Chronic indwelling catheters were implanted in the...
The renal excretion of meperidine by the fetus was determined in five chronic, unanesthesized fetal lamb preparations. Chronic indwelling catheters were implanted in the maternal aorta and vena cava, the fetal aorta, amniotic sac and allantoic sac. Via laparotomy, two catheters were implanted in the fetal bladder; the urachus and urethra were ligated. After intravenous administration of 2.5 mg/kg to the mother, meperidine rapidly appears in fetal urine. Approximately 0.02 to 0.05% of the maternal dose was excreted into fetal urine as unchanged meperidine in 300 min. The elimination half-life of meperidine in the fetus is 32.6 +/- 3.7 min when calculated from the urinary excretion rates, and 28.6 +/- 3.9 min when estimated from the plasma decay curve. The renal clearance of meperidine by the fetus ranged from 2.8 to 16.7 ml/min. Although the urachus and urethra were ligated, meperidine is found in samples of amniotic and allantoic fluid, indicating that the drug can diffuse across the placental membranes from the mother into these fluids. We have demonstrated that renal elimination of meperidine is a route of drug elimination by the fetus. These data support a pharmacokinetic model that describes the disposition of meperidine in the maternal-fetal unit by use of a two-compartment open model with elimination from both maternal and fetal compartments.
Topics: Animals; Female; Fetus; Kidney; Kinetics; Maternal-Fetal Exchange; Meperidine; Models, Biological; Pregnancy; Swine
PubMed: 439000
DOI: No ID Found -
Bioorganic & Medicinal Chemistry Dec 2010A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The...
A series of benzyl esters of meperidine and normeperidine were synthesized and evaluated for binding affinity at serotonin, dopamine and norepinephrine transporters. The 4-methoxybenzyl ester 8b and 4-nitrobenzyl ester 8c in the meperidine series and 4-methoxybenzyl ester 14a in the normeperidine series exhibited low nanomolar binding affinities at the SERT (K(i) values <2nM) and high SERT selectivity (DAT/SERT >1500 and NET/SERT >1500).
Topics: Esters; Ligands; Meperidine; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors; Structure-Activity Relationship
PubMed: 20980153
DOI: 10.1016/j.bmc.2010.09.060 -
Yao Xue Xue Bao = Acta Pharmaceutica... 1994Analytical methods of GC/FID and GC/MS for identification and determination of meperidine, an analgesic drug, and its metabolites were established. The determination of...
Analytical methods of GC/FID and GC/MS for identification and determination of meperidine, an analgesic drug, and its metabolites were established. The determination of meperidine spiked in urine was shown to have a good linear relationship in the range of 0.1-8.0 micrograms/ml urine (Y = 0.4995X + 0.1201, r = 0.9996). The detection limit was 20 ng/ml urine. With the developed methods, meperidine and its metabolites in urine collected from a meperidine addict were identified and determined. Meperidine, normeperidine, meperidinic acid in free and conjugate forms, normeperidine acid in free and conjugate forms, and acetyl-normeperidine were detected. Among these metabolites, acetyl-normeperidine was reported for the first time.
Topics: Cholinesterase Inhibitors; Chromatography; Gas Chromatography-Mass Spectrometry; Humans; Meperidine
PubMed: 8042511
DOI: No ID Found -
Soins. Cardiologie Jan 1984
Topics: Humans; Meperidine
PubMed: 6560825
DOI: No ID Found -
Anesthesia and Analgesia Aug 1987Meperidine has been used to suppress postanesthesia shivering. However, its efficacy to date has only been assessed by observation of visible shivering. We measured the... (Comparative Study)
Comparative Study
Meperidine has been used to suppress postanesthesia shivering. However, its efficacy to date has only been assessed by observation of visible shivering. We measured the effect of meperidine on oxygen consumption (VO2), carbon dioxide production (VCO2) and pulmonary gas exchange in 14 otherwise healthy patients shivering after general anesthesia. Meperidine successfully suppressed visible shivering in all patients and was associated with significant decreases in VO2, and VCO2 and minute ventilation (VE) but not with return to basal levels. Arterial PCO2 levels remained unchanged at normal, whereas significant improvements occurred in pH and bicarbonate levels. Meperidine is an effective method of reducing the elevated metabolic demand of shivering.
Topics: Acidosis; Anesthesia, General; Carbon Dioxide; Female; Humans; Male; Meperidine; Oxygen Consumption; Pulmonary Gas Exchange; Respiration; Shivering
PubMed: 3111305
DOI: No ID Found -
Journal of Basic and Clinical... 2009The likely effect of oral and subcutaneous meperidine on maximal electroshock seizure (MES) in mice was studied. Convulsive current fifty (CC50) was assessed to be 46m...
The likely effect of oral and subcutaneous meperidine on maximal electroshock seizure (MES) in mice was studied. Convulsive current fifty (CC50) was assessed to be 46m A, an electrical pulse causing seizure in 50% of test animals. Doses of 15, 30, 60, or 120 mg/kg meperidine given orally or subcutaneously increased the convulsion threshold of MES as evidenced by a significant dose-dependent reduction of MES below control value (p < .05). An initial hyperactivity reaction that was worsened by noisy and tactile stimuli and tail erection followed by sedation was observed after s.c. injection of 60 or 120 mg/kg meperidine. No significant difference was found between meperidine-induced reductions of control MES values obtained one and two hours after oral doses; the depressed MES values obtained one hour after oral administration of meperidine were significantly different and more powerful than those obtained two hours after s.c. drug administrations (p < .05). Combining previous literature information with the present results, we conclude that such an effect of meperidine can be attributed to cerebellar stimulation.
Topics: Administration, Oral; Animals; Cerebellar Cortex; Dose-Response Relationship, Drug; Electroshock; Female; Injections, Subcutaneous; Male; Meperidine; Mice; Narcotics; Seizures
PubMed: 19662718
DOI: 10.1515/jbcpp.2009.20.2.159 -
Canadian Anaesthetists' Society Journal Jan 1972
Topics: Adolescent; Adult; Aged; Analgesia; Blood Pressure; Female; Humans; Male; Meperidine; Methotrimeprazine; Middle Aged; Pain; Postoperative Care; Pulse; Respiration
PubMed: 5009452
DOI: 10.1007/BF03006912 -
Bioorganic & Medicinal Chemistry Letters Jun 2008Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-glycoprotein (P-gp), suggesting that up-regulation of P-gp may...
Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-glycoprotein (P-gp), suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of opioids. Addition of a 3-OH to meperidine and the ketone analog of meperidine yielding bemidone and ketobemidone, respectively, significantly increased P-gp substrate affinity. The results of this study have implications in the development of novel analgesics to be utilized as tools to study the contribution of P-gp on the development of central tolerance to opioids.
Topics: ATP Binding Cassette Transporter, Subfamily B; Drug Evaluation, Preclinical; Hydroxyl Radical; Meperidine; Molecular Structure; Receptors, Opioid; Stereoisomerism; Structure-Activity Relationship; Substrate Specificity
PubMed: 18499452
DOI: 10.1016/j.bmcl.2008.04.046 -
Journal of Clinical Pharmacology 1976The serum time-concentration curves and pharmacokinetic parameters of meperidine after the intravenous, intramuscular, and oral administration of 26 mg/m2 doses were...
The serum time-concentration curves and pharmacokinetic parameters of meperidine after the intravenous, intramuscular, and oral administration of 26 mg/m2 doses were determined and compared. After 30 minutes, there was no statistically significant difference between the serum time-concentration curve following intravenous administration and intramuscular administration; and after 2 hours, all three serum time-concentration curves were the same. Comparison of the mean cumulative excretion of meperidine and normeperidine following all three routes of administration demonstrated that the maxmimun rates of both meperidine and normeperidine reflect the route of administration, with a marked delay following oral administration reflecting a delay in absorption. Further, the excretion of normeperidene following oral administration, is greater despite adequate absorption than the other two routes of administration, indicating that delayed absorption increases the metabolic phase. Subjective symptomatology and the serum time-concentration curves were compared and their relationship wxamined. Comparison of the serum time-concentration curves to pervious analgesic and toxicity trials was made, and minimum serum levels for induction of analgesia and production of side effects are discussed. From the data it appears that in the case of acute pain, the intramuscular route of administration is as beneficial as the intravenous route, that oral dosing is less efficacious due to lower peak serum concentrations, and that all doses, regardless of the route administration, should be administered clinically on a mg/m2 basis rather than as a predetermined dose as currently used. Oral administration may have some benefit in the treatment of chronic pain, but the possibility of cumulative toxicity due to normeperidine should be considered.
Topics: Administration, Oral; Adult; Biotransformation; Chromatography, Gas; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Kinetics; Male; Meperidine
PubMed: 1262534
DOI: 10.1002/j.1552-4604.1976.tb02401.x