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PubMed2001

Buspirone and meperidine synergistically reduce the shivering threshold.

UNLABELLED: Mild hypothermia (i.e., 34 degrees C) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 degrees C while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 microg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 microg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer's solution at 4 degrees C. The control shivering threshold was 35.7 degrees C +/- 0.2 degrees C. The threshold was 35.0 degrees C +/- 0.8 degrees C during large-dose buspirone and 33.4 degrees C +/- 0.3 degrees C during large-dose meperidine. The threshold during the combination of the two drugs was 33.4 degrees C +/- 0.7 degrees C. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal PCO2 increased approximately 10 mm Hg with meperidine alone. Buspirone alone slightly reduced the shivering threshold. The combination of small-dose buspirone and small-dose meperidine acted synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. IMPLICATIONS: Mild hypothermia may be an effective treatment for acute stroke, but it usually triggers shivering, which could be harmful. Our results indicate that the combination of small-dose buspirone and small-dose meperidine acts synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. This combination may facilitate the induction of therapeutic hypothermia in stroke victims.

Adult↗
PubMed2001

A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients.

UNLABELLED: Tramadol is effective for treating shivering during epidural anesthesia in parturients. In addition to its low affinity to opioid receptors, tramadol exerts a modulatory effect on central monoaminergic pathways. In this respect, there are parallels between the mechanisms of the action of tramadol and antidepressants such as amitriptyline. Meperidine is often recommended for the treatment of postanesthetic shivering. This prospective, double-blinded, and randomized clinical study was performed to compare the antishivering effects and accompanying side effects among tramadol, meperidine, and amitriptyline for the treatment of postepidural anesthetic shivering. Forty-five parturients who shivered during cesarean delivery under epidural anesthesia and requested antishivering treatment were randomly allocated to one of three groups for IV treatment: Group T (n = 15) received tramadol 0.5 mg/kg, Group M (n = 15) received meperidine 0.5 mg/kg, and Group A (n = 15) received amitriptyline 15 or 20 mg. The response rate (shivering ceased after treatment in 15 min) was 87% and 93% for Groups T and M, respectively, compared with 13% in Group A (P < 0.01). The time that elapsed from treatment to the time shivering ceased was 5.1 +/- 3.6 min (mean +/- SD) for Group T and 4.2 +/- 2.3 min for Group M. There was a significantly more frequent incidence (33%) of somnolence in Group M when compared with Groups T (7%) and A (0%) (P < 0.01). However, no significant differences were shown for pruritus, nausea, vomiting, or Apgar scores of newborns. We concluded that both tramadol and meperidine show a significantly faster response rate in the treatment of postepidural anesthetic shivering when compared with amitriptyline in the dosage used; tramadol had a decreased incidence of somnolence when compared with meperidine. IMPLICATIONS: This study was performed to compare the antishivering and side effects among tramadol, amitriptyline, and meperidine for the treatment of postepidural anesthetic shivering in parturients. Both tramadol and meperidine show a significantly faster response rate in the treatment of shivering when compared with amitriptyline. Tramadol had a less frequent incidence of somnolence than meperidine.

Adolescent↗
PubMed1987

Pharmacokinetics of intrathecal morphine and meperidine in humans.

Two groups of surgical patients each comprising six individuals received an intrathecal injection of morphine 0.3 mg or meperidine 10 mg. Cerebrospinal fluid (CSF) and plasma were sampled frequently during a 6-h period and analyzed for morphine or meperidine. Maximum plasma morphine concentrations were found 5-10 min after injection, and averaged 4.5 +/- 1.1 ng.ml-1 (mean +/- SEM). Maximum CSF morphine concentrations were considerably higher than maximum plasma concentrations, 6410 +/- 1290 ng.ml-1. Maximum plasma concentrations of meperidine were also measured 5 or 10 min after injection and were low (36 +/- 9 ng.ml-1) compared with the maximum CSF concentrations (364 +/- 105 micrograms.ml-1). After a rapid initial decline for about 15 min after injection, the CSF concentrations decreased with a half-life of 89.8 +/- 16.1 min for morphine and 68.0 +/- 5.1 min for meperidine during the rest of the study period. The initial volume of distribution in CSF was similar for both drugs, or 22 +/- 8 ml for morphine and 18 +/- 5 ml for meperidine. After 6 h, 1.6 +/- 0.9% of the injected morphine dose and 0.41 +/- 0.09% of the meperidine dose remained in the initial volume of distribution. Large inter-individual differences in morphine and meperidine CSF kinetics existed, which may explain some of the reported individual differences in duration of effects. The disappearance of meperidine from CSF tended to be faster than that of morphine, which may be explained, in part, by the differences in lipid solubilities of the drugs.

Adult↗
PubMed1998

The effects of meperidine and sufentanil on the shivering threshold in postoperative patients. pascal.alfonsi@apr.ap-hop-paris.fr.

UNLABELLED: BACKGROUND. Meperidine (pethidine) reportedly treats postoperative shivering better than equianalgesic doses of other mu-receptor agonists. The authors' first goal was to develop a method to accurately determine postoperative shivering thresholds, and then to determine the extent to which meperidine and sufentanil inhibit postoperative shivering. METHODS: A computer-controlled infusion was started before operation in 30 patients, with target plasma concentrations of 0.15, 0.30, or 0.60 microg/ml meperidine or 0.1, 0.15, or 0.2 ng/ ml sufentanil targeted; patients were randomly assigned to each drug and concentration. The infusion was continued throughout surgery and recovery. Anesthesia was maintained with nitrous oxide and isoflurane. Core temperatures were approximately 34 degrees C by the end of surgery. The compensated core temperature at which visible shivering and a 20% decrease in steady-state oxygen consumption was recorded identified the shivering threshold. A blood sample for opioid concentration was obtained from each patient at this time. The ability of each opioid to reduce the shivering threshold was evaluated using linear regression. RESULTS: End-tidal isoflurane concentrations were <0.2% in each group at the time of extubation, and shivering occurred approximately 1 h later. Meperidine linearly decreased the shivering threshold: threshold (degrees C) = -2.8 x [meperidine (microg/ml)] + 36.2; r2 = 0.64, P = 0.0005. Sufentanil also linearly decreased the shivering threshold: threshold (degrees C) = -7.8 x [sufentanil (ng/ ml)] + 36.9; r2 = 0.46, P = 0.02. CONCLUSIONS: At a given dose, sufentanil inhibited shivering 2,800 times better than meperidine. However, the equianalgesic ratio of these drugs is approximately 4,900. That is, meperidine inhibited shivering better than would be expected based on the equianalgesic potency ratio. These data are thus consistent with clinical observations suggesting that meperidine indeed possesses special antishivering activity.

Adult↗
PubMed2000

Tonic blocking action of meperidine on Na+ and K+ channels in amphibian peripheral nerves.

BACKGROUND: Among opioids, meperidine (pethidine) also shows local anesthetic activity when applied locally to peripheral nerve fibers and has been used for this effect in the clinical setting for regional anesthesia. This study investigated the blocking effects of meperidine on different ion channels in peripheral nerves. METHODS: Experiments were conducted using the outside-out configuration of the patch-clamp method applied to enzymatically prepared peripheral nerve fibers of Xenopus laevis. Half-maximal inhibiting concentrations were determined for Na+ channels and different K+ channels by nonlinear least-squares fitting of concentration-inhibition curves, assuming a one-to-one reaction. RESULTS: Externally applied meperidine reversibly blocked all investigated channels in a concentration-dependent manner, i.e., voltage-activated Na+ channel (half-maximal inhibiting concentration, 164 microM), delayed rectifier K+ channels (half-maximal inhibiting concentration, 194 microM), the calcium-activated K+ channel (half-maximal inhibiting concentration, 161 microM), and the voltage-independent flicker K+ channel (half-maximal inhibiting concentration, 139 microM). Maximal block in high concentrations of meperidine reached 83% for delayed rectifier K+ channels and 100% for all other channels. Meperidine blocks the Na+ channel in the same concentration range as the local anesthetic agent lidocaine (half-maximal inhibiting concentration, 172 microM) but did not compete for the same binding site as evaluated by competition experiments. Low concentrations of meperidine (1 nM to 1 microM) showed no effects on Na+ channels. The blockade of Na+ and delayed rectifier K+ channels could not be antagonized by the addition of naloxone. CONCLUSIONS: It is concluded that meperidine has a nonselective inhibitory action on Na+ and K+ channels of amphibian peripheral nerve. For tonic Na+ channel block, neither an opioid receptor nor the the local anesthetic agent binding site is the target site for meperidine block.

Analgesics, Opioid↗
PubMed2004

Meperidine suppresses the excitability of spinal dorsal horn neurons.

BACKGROUND: In addition to local anesthetics, meperidine has been successfully used for local anesthesia. When applied intrathecally, the dorsal horn neurons of the superficial laminae are exposed to high concentrations of meperidine. These cells represent an important point for the transmission of pain information. This study investigated the blocking effects of meperidine on different ionic currents of spinal dorsal horn neurons and, in particular, its impact on the generation of action potentials. METHODS: Using a combination of the patch clamp technique and the entire soma isolation method, the action of meperidine on voltage-gated Na+ and K+ currents in spinal dorsal horn neurons of rats was described. Current clamp recordings from intact neurons showed the functional relevance of the ion current blockade for the generation of action potentials. RESULTS: Externally applied meperidine reversibly blocked voltage-gated Na+ currents with a half-maximum inhibiting concentration (IC50) of 112 microM. During repetitive stimulation, a slight phasic block occurred. In addition, A-type K+ currents and delayed-rectifier K+ currents were affected in a dose-dependent manner, with IC50 values of 102 and 52 microM, respectively. In the current clamp mode, single action potentials were suppressed by meperidine. The firing frequency was lowered to 54% at concentrations (100 microM) insufficient for the suppression of a single action potential. CONCLUSIONS: Meperidine inhibits the complex mechanism of generating action potentials in spinal dorsal horn neurons by the blockade of voltage-gated Na+ and K+ channels. This can contribute to the local anesthetic effect of meperidine during spinal anesthesia.

Action Potentials↗
PubMed2003

Dexmedetomidine and meperidine additively reduce the shivering threshold in humans.

BACKGROUND AND PURPOSE: Hypothermia might prove to be therapeutically beneficial in stroke victims; however, even mild hypothermia provokes vigorous shivering. Meperidine and dexmedetomidine each linearly reduce the shivering threshold (triggering core temperature) with minimal sedation. We tested the hypothesis that meperidine and dexmedetomidine synergistically reduce the shivering threshold without producing substantial sedation or respiratory depression. METHODS: We studied 10 healthy male volunteers (18 to 40 years) on 4 days: (1) control (no drug); (2) meperidine (target plasma level 0.3 microg/mL); (3) dexmedetomidine (target plasma level 0.4 ng/mL); and (4) meperidine plus dexmedetomidine (target plasma levels of 0.3 microg/mL and 0.4 ng/mL, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused through a central venous catheter to decrease tympanic membrane temperature by approximately 2.5 degrees C/h; mean skin temperature was maintained at 31 degrees C. An increase in oxygen consumption >25% of baseline identified the shivering threshold. Sedation was evaluated by using the Observer's Assessment of Sedation/Alertness scale. Two-way repeated-measures ANOVA was used to identify interactions between drugs. Data are presented as mean+/-SD; P<0.05 was statistically significant. RESULTS: The shivering thresholds on the study days were as follows: control, 36.7+/-0.3 degrees C; dexmedetomidine, 36.0+/-0.5 degrees C (P<0.001 from control); meperidine, 35.5+/-0.6 degrees C (P<0.001); and meperidine plus dexmedetomidine, 34.7+/-0.6 degrees C (P<0.001). Although meperidine and dexmedetomidine each reduced the shivering threshold, their interaction was not synergistic but additive (P=0.19). There was trivial sedation with either drug alone or in combination. Respiratory rate and end-tidal Pco2 were well preserved on all days. CONCLUSIONS: Dexmedetomidine and meperidine additively reduce the shivering threshold; in the small doses tested, the combination produced only mild sedation and no respiratory toxicity.

Adolescent↗
PubMed1993

Meperidine-related seizures associated with patient-controlled analgesia pumps.

OBJECTIVE: To report three cases of meperidine-related seizures when meperidine was administered via patient-controlled analgesia pump (PCAP) and to review literature related to meperidine-associated seizures. DATA SOURCES: Case reports and review articles identified by a computerized search (MEDLINE) and manual search (Index Medicus). DATA SYNTHESIS: PCAPs are being used frequently to relieve the pain of sickle cell crisis as well as pain from many other etiologies. We report three cases of meperidine-related seizures associated with its administration via PCAP. Each of the patients received either relatively high doses, long-term therapy, or both. Meperidine has been associated with seizure activity when administered via traditional routes. Previously identified risk factors for the development of meperidine-related seizures include renal failure, high meperidine dosages, and coadministration of hepatic enzyme-inducing medications or phenothiazines. CONCLUSIONS: Meperidine administered via PCAP may be associated with seizures. Optimally, an alternative analgesic should be administered when this route is used.

Adult↗
PubMed1997

Site-specific pharmacokinetics and pharmacodynamics of intramuscular meperidine in elderly postoperative patients.

OBJECTIVE: To examine and compare the pharmacokinetics and pharmacodynamics of meperidine when administered intramuscularly at gluteal and deltoid sites in elderly postoperative patients. DESIGN: Prospective, randomized investigation. SETTING: Tertiary care university teaching hospital. PATIENTS: Fourteen patients 60 years of age or older who were undergoing general surgery. INTERVENTION: A single dose of meperidine 0.75 mg/kg given intramuscularly at either a deltoid or gluteal site. MAIN OUTCOME MEASURES: Pharmacokinetic (based on concentration-time curves) and pharmacodynamic (i.e., pain scales, need for additional pain medication) comparisons were made, based on site of meperidine injection. RESULTS: No statistically significant differences were found in the maximum plasma concentration, volume of distribution, or clearance of meperidine by site of injection. Substantial interpatient variability in pharmacokinetic parameters was noted for both sites (range of maximum concentrations: 191-500 ng/mL gluteal, 166-374 ng/mL deltoid). Although pain scores were similar for the two groups, four of the patients in the group given gluteal injection required additional breakthrough pain management within 4 hours of meperidine injection compared with one patient in the group given deltoid injection. CONCLUSIONS: There is no obvious relationship between meperidine pharmacokinetic and pharmacodynamic parameters, regardless of intramuscular injection site. Breakthrough pain is common when patients are given intramuscular injections postoperatively, particularly when the gluteal route is used. When meperidine is used for analgesia in elderly postoperative patients, consideration should be given to more rapid and predictable routes (e.g., intravenous injection) of meperidine administration.

Aged↗
PubMed2005

The effect of meperidine on thermoregulation in mice: involvement of alpha2-adrenoceptors.

Meperidine has potent antishivering properties. The underlying mechanisms are not fully elucidated, but recent investigations suggest that alpha2-adrenoceptors are likely to be involved. We performed the current study to investigate the effects of meperidine on nonshivering thermogenesis in a model of thermoregulation in mice. After injection (0.1 mL/kg intraperitoneally) of saline, meperidine (20 mg/kg), the specific alpha2-adrenoceptor antagonist atipamezole (2 mg/kg), plus saline or atipamezole plus meperidine, respectively, mice were positioned in a Plexiglas chamber. Rectal temperature and mixed expired carbon dioxide were measured after provoking thermoregulatory effects by whole body cooling. Maximum response intensity of nonshivering thermogenesis and the thermoregulatory threshold for nonshivering thermogenesis, which was defined as the temperature at which a sustained increase in expiratory carbon dioxide can be measured, were investigated. Meperidine significantly decreased the threshold of nonshivering thermogenesis (36.6 degrees C +/- 0.7 degrees C) versus saline (37.9 degrees C +/- 0.6 degrees C) and versus atipamezole plus saline (37.8 degrees C +/- 0.4 degrees C; P <0.01). This effect was abolished after administration of meperidine combined with atipamezole (37.7 degrees C +/- 0.6 degrees C; P <0.05). Meperidine did not decrease the maximum intensity of nonshivering thermogenesis. The results suggest a major role of alpha2-adrenoceptors in the inhibition of thermoregulation by meperidine in mice.

Adrenergic alpha-Antagonists↗
PubMed1983

Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination.

As part of a study to evaluate the analgesic efficacy of meperidine and hydroxyzine, alone and in combination, a double-blind complete crossover study of meperidine (50 mg IM), hydroxyzine (100 mg IM), meperidine (50 mg IM) plus hydroxyzine (100 mg IM), and saline placebo was conducted. Thirty patients with chronic moderate to severe pain due to metastatic cancer were evaluated as to pain relief following administration of all four study medications. All of the treatment groups showed statistically significant analgesic activity as compared to placebo. Hydroxyzine provided sustained pain relief to six hours, whereas meperidine produced analgesia up to two hours. The combination produced additive analgesia only during the first 2 hr. The pharmacokinetics of meperidine and hydroxyzine were compared to observed analgesia. Significant correlation between serum drug levels of meperidine and hydroxyzine and pain relief resulted and the serum levels of meperidine and hydroxyzine necessary for analgesia were calculated to be 0.10-0.15 mg/ml and 60-70 ng/ml; respectively. The observed analgesia of the meperidine/hydroxyzine combination was correlated with the analgesia of the individual agents and the limited additive analgesia observed with the addition of meperidine to hydroxyzine does not justify the added toxicity of the narcotic.

Aged↗
PubMed2000

[Usefulness of meperidine in anesthesiology].

Meperidine was the first synthetic opioid agent. It acts mainly as an antagonist of mu (#m) receptors and has an analgesic potency ten times greater than that of morphine. Like other opioid drugs, meperidine causes nausea, vomiting, urinary retention and respiratory depression; a point of difference, however, is that it acts on nerve fibers and has properties similar to those of local anesthetics. It has therefore been used as an alternative to other opioids for anesthetic blockade. We review the indications and contraindications of meperidine administered by different routes. For pain, epidural administration has proven to be a good alternative to intravenous administration and epidural meperidine has been combined with local anesthetics using lower doses of both drugs and producing fewer side effects. Intradural meperidine has been used as the sole anesthetic agent in various types of surgery, its principal advantage being that it provides long-lasting postoperative analgesia. Spinal meperidine has the advantage over morphine of a lower incidence of respiratory depression, particularly late-occurring depression. An intravenous route has been used for treating moderate to severe pain, for regional anesthesia, for premedication and for analgesia during anesthesia. Meperidine's action on kappa receptors has meant that it is considered the most effective drug for treating postanesthetic trembling. Although meperidine has been used effectively to treat non-surgical pain, mainly from colic, this review focuses on its usefulness in the perioperative period.

Adjuvants, Anesthesia↗
PubMed2004

CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes.

Meperidine is an opioid analgesic metabolized in the liver by N-demethylation to normeperidine, a potent stimulant of the central nervous system. The purpose of this study was to identify the human cytochrome P450 (P450) enzymes involved in normeperidine formation. 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. After normalization by its relative abundance in human liver microsomes, CYP2B6, CYP3A4, and CYP2C19 accounted for 57, 28, and 15% of the total intrinsic clearance of meperidine. CYP3A5 and CYP2D6 contributed to < 1%. Formation of normeperidine significantly correlated with CYP2B6-selective S-mephenytoin N-demethylation (r = 0.88, p < 0.0001 at 75 > microM meperidine, and r = 0.89, p < 0.0001 at 350 microM meperidine, n = 21) and CYP3A4-selective midazolam 1'-hydroxylation (r = 0.59, p < 0.01 at 75 microM meperidine, and r = 0.55, p < 0.01 at 350 microM meperidine, n = 23). No significant correlation was observed with CYP2C19-selective S-mephenytoin 4'-hydroxylation (r = 0.36, p = 0.2 at 75 microM meperidine, and r = 0.02, p = 0.9 at 350 microM meperidine, n = 13). An anti-CYP2B6 antibody inhibited normeperidine formation by 46%. In contrast, antibodies inhibitory to CYP3A4 and CYP2C8/9/18/19 had little effect (<14% inhibition). Experiments with thiotepa and ketoconazole suggested inhibition of microsomal CYP2B6 and CYP3A4 activity, whereas studies with fluvoxamine (a substrate of CYP2C19) were inconclusive due to lack of specificity. We conclude that normeperidine formation in human liver microsomes is mainly catalyzed by CYP2B6 and CYP3A4, with a minor contribution from CYP2C19.

Aryl Hydrocarbon Hydroxylases↗
PubMedDate not supplied

GABAmimetics diminish antinociception of meperidine under conditions which enhance other opioid mu-agonists.

This study investigated the effects of pretreatment with muscimol (GABA-agonist) or diazepam (indirect GABAmimetic) on i.v. meperidine, fentanyl, alphaprodine and morphine, using rabbit tooth pulp and mouse hot plate assays. A previous study reported that the ED50 values for fentanyl in rabbits were significantly lowered by 0.25 mg/kg of muscimol (13.8 to 1.8 micrograms/kg) and by 1.5 mg/kg of diazepam (13.1 to 1.1 micrograms/kg). ED50 values for meperidine in rabbits in this study were increased by muscimol (1.2 to 3.2 mg/kg) and diazepam (1.5 to 3.1 mg/kg). ED50 values for fentanyl in mice were significantly lowered by 0.25 mg/kg of muscimol (23.0 to 8.9 micrograms/kg) and 1.0 mg/kg of diazepam (23.3 to 12.8 micrograms/kg). ED50 values for meperidine in mice were significantly increased by muscimol (2.1 to 5.0 mg/kg) and diazepam (2.0 to 4.8 mg/kg). ED50 values for alphaprodine and morphine were significantly lowered by muscimol and diazepam in mice. A higher dose of muscimol (1.0 mg/kg) had no effect on the ED50 values of meperidine in mice. The antinociception of a submaximal dose of meperidine in rabbits was significantly reduced by a 10 min pretreatment with i.v. diazepam (1.5 mg/kg) at 15, 20, 30 and 45 min after i.v. meperidine. The antinociception of a submaximal dose of fentanyl in rabbits was significantly increased by a 10 min pretreatment with i.v. diazepam (1.5 mg/kg) at 5, 10, 15 and 20 min after i.v. fentanyl. Pretreatment with 0.1 mg/kg of scopolamine enhanced the antinociceptive effect of a submaximal dose of fentanyl in both animal models. Diazepam reduced the antinociception produced by the combination scopolamine-fentanyl to that of fentanyl-vehicle control in both animal models. Pretreatment with 0.1 mg/kg of scopolamine did not change the magnitude of antinociception of a submaximal dose of meperidine in rabbits. Since meperidine possesses inherent anticholinergic activity, it is suggested that this anticholinergic activity may be involved in the reduction effects by muscimol and diazepam.

Alphaprodine↗
PubMed1979

Urinary excretion of meperidine by the fetal lamb.

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.

Animals↗
PubMedDate not supplied

Renal N-oxidation of meperidine by the perfused kidney of the rat.

Isolated perfused kidneys of rats were used to determined renal metabolism of meperidine and its relation to meperidine excretion. Starting perfusate concentrations of meperidine were 18.4 and 190 micrograms/ml, and resulted in respective nonsaturation and saturation kinetics for removal of meperidine. Disposition of 14C-meperidine was followed and supplemented with measurements of meperidine by gas chromatography. A major renal metabolite was shown to facilitate the renal excretion of meperidine. This metabolite was identified by gas chromatography/mass spectrometry as the N-oxide of meperidine.

Animals↗
PubMed1982

Epidural meperidine-bupivacaine for obstetric analgesia.

In 13 full-term primipara in active labor an initial single dose of preservative-free meperidine (100 mg) diluted in 10 ml of saline was injected epidurally (L2-3). In another 13 full-term parturients in active labor, 10 ml of bupivacaine 0.25% was used. Pain was scored by the linear analog scale. Onset of analgesia was 5.3 +/- 2.8 minutes following administration of meperidine, and 12.9 +/- 6.9 minutes following bupivacaine (p less than 0.01). Pain score decreased to 0 in 12 of 13 patients following meperidine administration and in six of 13 patients following bupivacaine (p less than 0.01). Satisfactory analgesia lasted 160.8 +/- 90.3 minutes following meperidine, and 103.5 +/- 42 minutes following bupivacaine administration (p less than 0.01). Subsequent supplementation by intermittent doses of 10 ml of bupivacaine 0.25% was more effective and less frequent following meperidine than following bupivacaine administration. Maternal sedation, nausea, and itching occurred frequently following administration of epidural meperidine, whereas hypotension, numbness, and motor dysfunction followed bupivacaine. In neither group was significant respiratory depression observed. All parturients delivered vaginally, 288 +/- 212.6 minutes following meperidine and 348 +/- 195.8 minutes following bupivacaine administration (p greater than 0.05); the neonates showed normal Apgar scores and neurobehavioral responses. Epidural meperidine, supplemented by subsequent bupivacaine as indicated, provides maternal sedation and satisfactory analgesia, and it diminishes the requirements of bupivacaine supplementation. The technique is advantageous in the parturient primipara.

Adolescent↗
PubMed1980

Renal tubular secretion of meperidine by the fetal lamb.

We have determined the renal clearance of meperidine and inulin simultaneously under steady-state conditions by using the chronic fetal lamb preparation. Meperidine was infused at a constant rate of 3.2 mg/min into the maternal vena cava, and [14C]inulin was infused at a constant rate of 0.22 muCi/min into the fetal vena cava. Total fetal urine output was collected for three consecutive 15-min intervals, and fetal blood was sampled at the midpoint of each urine collection. The mean meperidine clearance in 12 studies was 12.04 +/- 2.90 (S.E.) ml/min, whereas mean inulin clearance was 2.48 +/- 0.35 (S.E.) ml/min. In all but one animal, the ratio of meperidine clearance to inulin clearance is greater than one, indicating tubular secretion of meperidine. The results show that there is a negative relationship between meperidine clearance and urine pH, but there is no relationship between meperidine clearance and gestational age or urine flow rate. These results suggest that meperidine is secreted across the renal tubules by "ion trapping."

Animals↗