Disease relevance of Pethidine - Intermediate-B

• Normeperidine levels were 0.05 to 0.28 microng/ml in the cancer patients and 0.13 to 0.36 in the renal failure patients [1].
• In 48 patients, excitatory effects ranging from mild nervousness to tremors, twitches, multifocal myoclonus, and seizures were directly correlated with accumulation of normeperidine in plasma [2].
• Plasma concentrations and 24-hr urinary excretion of normeperidine was lower and persistence of normeperidine in plasma longer in the patients with cirrhosis [3].
• Heroin, d-propoxyphene and meperidine produced nonlethal clonic seizures, whereas normeperidine and thebaine produced tonic-clonic seizures which were followed by death [4].
• Normeperidine toxicity [5].

High impact information on Pethidine - Intermediate-B

• The ratio of normeperidine to meperidine levels was always higher in the renal failure patients than in the cancer patients [1].
• The effects of route of administration and altered urinary pH on the disposition of meperidine and its metabolite normeperidine were investigated in six normal, nonsmoking young men from 23 to 31 yr old [6].
• Patients with cirrhosis may be relatively protected from normeperidine toxicity because of impaired formation, but the risk of cumulative toxicity may be greater than in normal subjects because of slower elimination of the metabolite and greater sensitivity to the effects of narcotics on the central nervous system [3].
• A comparison of 50, 100 and 200 mg of intra-articular pethidine during knee joint surgery, a controlled study with evidence for local demethylation to norpethidine [7].
• Breast milk specimens, obtained at 12, 24, 36, 48, 72, and 96 h postpartum and analyzed for opioids and metabolites, showed persistently elevated normeperidine concentrations in the meperidine group [8].

Chemical compound and disease context of Pethidine - Intermediate-B

• Furthermore, convulsions have been associated with normeperidine and cardiac toxicities with norpropoxyphene [9].

Biological context of Pethidine - Intermediate-B

• A second group, consisting of buprenorphine, nalbuphine and l-pentazocine, produced only a naloxone-sensitive increase in body temperature, whereas the group comprising ethylketazocine, ketazocine, l-cyclazocine and normeperidine caused only a decrease [10].
• The pharmacokinetics of pethidine (meperidine) and norpethidine (normeperidine) have been investigated after iv administration of pethidine in the rat [11].
• Pethidinic and norpethidinic acids, and their conjugated metabolites (after beta-glucuronidase treatment) were determined after conversion into pethidine and norpethidine by acid-catalysed esterification [12].
• Statistical analysis of the data showed no significant difference between the urine concentrations of meperidine and normeperidine produced by either preparation, and the preparations are of comparable bioavailability [13].
• We report three cases of norpethidine toxicity in patients receiving pethidine by PCA [14].

Anatomical context of Pethidine - Intermediate-B

• The study suggests that multiple doses to the mother over long time periods result in maximum accumulation of both meperidine and normeperidine in fetal tissues [15].
• Our in vitro studies included 1) screening 16 expressed P450s for normeperidine formation, 2) kinetic experiments on human liver microsomes and candidate P450s, and 3) correlation and inhibition experiments using human hepatic microsomes [16].
• Normeperidine was not detected in either maternal plasma or amniotic fluid during the time course of this study [17].
• The results show surprisingly high concentrations of both meperidine and normeperidine in fetal blood at delivery [15].
• In addition, the amount of normeperidine increased with time in umbilical cord blood, the ratio of normeperidine to meperidine increased with time, and the umbilical artery-to-vein ratio of meperidine (but not normeperidine) was greater than one following long drug-to-delivery intervals [15].

Associations of Pethidine - Intermediate-B with other chemical compounds

• Radioimmunoassay for normeperidine: studies on the N-dealkylation of meperidine and anileridine [18].
• The plasma and cerebrospinal fluid (CSF) concentrations of pethidine and its main metabolite in plasma, norpethidine, were determined in 20 patients undergoing minor surgery who had received pethidine chloride as premedication in a standard dose of 100 mg intramuscularly [19].

Gene context of Pethidine - Intermediate-B

• An anti-CYP2B6 antibody inhibited normeperidine formation by 46% [16].
• The purpose of this study was to identify the human cytochrome P450 (P450) enzymes involved in normeperidine formation [16].

Analytical, diagnostic and therapeutic context of Pethidine - Intermediate-B

• In our study gas chromatography was used to determine the concentrations of meperidine and normeperidine in the plasma and urine of pregnant and nonpregnant women and in the urine of neonates [20].
• The results suggest that in patients requiring repeated meperidine dosage the drug should be taken parenterally rather than orally to allow maximal analgesia and minimal formation of normeperidine [3].
• A sensitive and specific radioimmunoassay for normeperidine has been developed that can detect as little as 100 pg of this metabolite [18].
• Norpethidine toxicity and patient controlled analgesia [14].
• Oral administration may have some benefit in the treatment of chronic pain, but the possibility of cumulative toxicity due to normeperidine should be considered [21].

References