Morphine Metabolism in Neonates and Infants

Choonara, I A; Lawrence, Andrew J.; Michalkiewicz, A.; Bowhay, A.; Ratcliffe, J.

doi:10.1097/00132586-199306000-00040

Cited by 15 publications

(26 citation statements)

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“…In support of this is the presence of enzyme activity toward morphine in human fetal kidney ; however, in the fetus, metabolites excreted in urine are likely to eventually enter the circulation through swallowing of amniotic fluid. Moreover, clearance of morphine and M3G in the human neonate is quantitatively very low, making it unlikely that renal clearance is a major contributor in utero (Choonara et al, 1992;Hartley et al, 1993b). Another consideration would be the formation of metabolites other than monoglucuronides.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there are marked differences in morphine clearance between infant and adult humans (Gerdin et al, 1990c;Choonara et al, 1992;Hartley et al, 1993b;Milne et al, 1996). In pregnant women, morphine clearance is 42 ml ⅐ min Ϫ1 ⅐ kg Ϫ1 , whereas in premature and term newborn infants, total morphine clearance ranges from 1 to 10 ml ⅐ min Ϫ1 ⅐ kg Ϫ1 .…”

Section: Garland Et Almentioning

confidence: 99%

“…If indeed the clearances do decrease with dose, this cannot be explained by saturation of fetal metabolism; however, it could reflect saturation of a placental transport mechanism. The therapeutic concentrations of morphine reported in new- dmd.aspetjournals.org born infants are usually between 100 to 150 ng ⅐ ml Ϫ1 , although levels in excess of 400 ng ⅐ ml Ϫ1 have been reported (Chay et al, 1992;Choonara et al, 1992;Hartley et al, 1993b). Mechanisms other than saturation of metabolism will need to be evaluated if results from paired infusion studies of morphine reveal the same discrepancies in placental clearances, since these studies are conducted in the therapeutic range.…”

Section: Fetal Metabolism Of Morphinementioning

confidence: 99%

“…M6G is found in human neonates but was not found in the sheep fetus (Olsen et al, 1988;Choonara et al, 1992;Hartley et al, 1993b). In the fetal baboon, the concentration of M3G is 22 times that of M6G, whereas, in the adult baboon, the ratio is in the order of 40 times (Garland et al, 2001).…”

Section: Fetal Metabolism Of Morphinementioning

confidence: 99%

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The Contribution of Fetal Metabolism to the Disposition of Morphine

Garland¹,

Abildskov²,

Kiu³

et al. 2004

Drug Metab Dispos

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ABSTRACT:The contribution of fetal metabolism to drug disposition in pregnancy is poorly understood. With maternal administration of morphine, like many drugs, steady-state concentrations in fetal plasma are less than in maternal plasma. The contribution of fetal metabolism to this difference is unknown. Morphine was used as a model drug to test the hypothesis that fetal metabolism contributes sig- The safe and effective use of drugs during pregnancy requires detailed knowledge of drug disposition and action in both the mother and the fetus. Changes in distribution, clearance, and effect in the mother can be studied in a clinical population during therapeutic use of a drug (Gerdin et al., 1990c;O'Sullivan et al., 1993); however, mothers and clinicians are primarily concerned about any adverse effects of pharmacological agents on the developing fetus. This makes it equally if not more important to develop an in-depth understanding of the bioavailability of drugs to the fetus. It is obviously not possible to perform detailed pharmacological studies in the human fetus (Gerdin et al., 1990b). A nonhuman primate model provides an opportunity to delineate disposition pathways of drug and metabolite from which relevant parallels can be drawn to human pregnancy. Similarities between human and nonhuman primate pregnancy include endocrinology of pregnancy, structure and function of the placenta, metabolism of drugs, and fetal cardiorespiratory and neurobehavioral development (Dvorchik et al

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Section: Discussionmentioning

confidence: 99%

Section: Garland Et Almentioning

confidence: 99%

Section: Fetal Metabolism Of Morphinementioning

confidence: 99%

Section: Fetal Metabolism Of Morphinementioning

confidence: 99%

See 2 more Smart Citations

The Contribution of Fetal Metabolism to the Disposition of Morphine

Garland¹,

Abildskov²,

Kiu³

et al. 2004

Drug Metab Dispos

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“…Reduced plasma protein levels (especially alpha-1-acid glycoprotein) [25] may result in high levels of free drug. There are also potential differences in the proportion of subclasses of opioid receptors [26] as well as differences in the ratio of the production of the morphine glucuronides [27]. All these factors are involved in neonatal opioid sensitivity, but they should not preclude the use of opioids in spontaneously breathing neonates.…”

mentioning

confidence: 99%

Assessment and control of pain in children

Lloyd-Thomas

1995

Anaesthesia

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Pharmacokinetic and pharmacodynamic study of morphine and morphine 6‐glucuronide after oral and intravenous administration of morphine in children with cancer

Mashayekhi

Ghandforoush-Sattari

Routledge

et al. 2009

Biopharm & Drug Disp

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The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6-glucuronide (M6G) in children with cancer. Serum concentrations of morphine and M6G in children who received single oral or short term continuous intravenous morphine were determined by HPLC and ELISA assays, respectively. The serum C(max) of morphine and M6G after i.v. morphine administration was 560.5 and 309.0 nM and the T(max) was 61 and 65 min, respectively. The elimination half-life was 140.0 and 328.7 min, respectively. After oral administration of morphine, the serum C(max) of morphine and M6G was 408.34 and 256.3 nM and the T(max) was 40.0 and 60 min, respectively. The half-life was 131.0 and 325.8 min, respectively. The side effects were: drowsiness (100%), nausea and/or vomiting (57%), pruritus (28%) and urinary retention (14%). There were no reports of respiratory complications. This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur.

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Morphine Metabolism in Neonates and Infants

Cited by 15 publications

References 0 publications

The Contribution of Fetal Metabolism to the Disposition of Morphine

The Contribution of Fetal Metabolism to the Disposition of Morphine

Assessment and control of pain in children

Pharmacokinetic and pharmacodynamic study of morphine and morphine 6‐glucuronide after oral and intravenous administration of morphine in children with cancer

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