Disposition of Morphine in Man

Spector, Sydney; Vesell, E S

doi:10.1126/science.174.4007.421

Cited by 62 publications

(14 citation statements)

References 7 publications

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“…From the studies of Spector and Vesell (Fig. I ) 20 and Brunk and Delle (Fig. 1), 2 the apparent volume of distribution (Vd) of morphine after parenteral administration to man can be esti- mated by extrapolation of the plasma decay curve from 1 to 6 hr to the zero time, multiplying this plasma concentration by 0.65 to obtain the free drug concentration, and dividing the dose by the free plasma morphine concentration.…”

Section: Discussionmentioning

confidence: 99%

Morphine and phenytoin binding to plasma proteins in renal and hepatic failure

Olsen

Bennett

Porter

1975

Clin Pharma and Therapeutics

161

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The binding of morphine and phenytoin to plasma proteins was examined in healthy subjects and in patients with renal and hepatic failure. In the uremic patients without hepatic failure, morphine binding was dependent on the concentration of total serum proteins and albumin, but not the severity of renal failure as measured by creatinine clearance. Binding of phenytoin, however, was dependent on the degree of renal failure and albumin concentration, but not on total serum protein concentration. Renal transplant in 1 patient restored the binding of both drugs to a value within the normal range. The combination of hypoalbuminemia and hyperbilirubinemia resulted in the greatest impairment to binding for both drugs. It is concluded that patients with uremia, jaundice, hypoalbuminemia, particularly in combination, are sensitive to usual clinical doses of morphine, at least in part, because of decreased binding to plasma proteins.

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Section: Discussionmentioning

confidence: 99%

Morphine and phenytoin binding to plasma proteins in renal and hepatic failure

Olsen

Bennett

Porter

1975

Clin Pharma and Therapeutics

161

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“…Morphine pharmacokinetics have been assessed in recent studies using both radiolabeled morphine 4 and unlabeled morphine quantitated in blood by radioimmunoassay.2, [17][18][19] Using the immunoassay technique, 16,17 we extended previous studies by assessing the rate and completeness of absorption of intramuscular mor-phine given in usual therapeutic doses. We also studied the pharmacokinetics of high-dose morphine given intravenously to elderly patients with cardiovascular disease undergoing extensive surgical procedures.…”

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confidence: 99%

“…puncture, at the end of the infusion and at 1, 2, 3,5, 10, 15,30,45 min, 1 hr, 1. 5,2,3,4,6,8,12,18,24,32, and 48 hr following the end of the infusion. Plasma was separated and frozen until the time of assay.…”

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confidence: 99%

Kinetics of intravenous and intramuscular morphine

Stanski

Greenblatt

Lowenstein

1978

Clin Pharma and Therapeutics

227

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The disposition of parenteral morphine was assessed in two pharmacokinetic studies. In Study 1, 10 mg of morphine sulfate was administered by intravenous (IV) infusion, intramuscular (IM) injection, or both, to 8 healthy young adult male volunteers. Plasma morphine concentrations were determined by radioimmunoassay in multiple blood samples drawn after each dose. Mean (+/-SE) kinetic parameters following IV morphine were: volume of distribution (Vd), 3.2 (+/- 0.3) L/kg; elimination half-life (t1/2beta), 2.9 (+/- 0.5) hr; clearance, 14.7 (+/- 0.9) ml/min/kg; extraction ratio, 0.70 (+/- 0.04). After IM morphine, peak plasma levels ranged from 51 to 62 ng/ml and were reached within 20 min of injection. The absorption half-life averaged 7.7 (+/- 1.6) min. Systemic availability was 100% complete. In study 2, 4 elderly male patients (61 to 80 yr of age) received 45 to 80 mg of morphine sulfate IV prior to operative repair of an abdominal aortic aneurysm. Morphine pharmacokinetics were determined as described above. Kinetic variables were Vd, 4.7 (+/- 0.2) L/kg; t1/2beta, 4.5 (+/- 0.3) hr; clearance, 12.4 (+/- 1.2) ml/min/kg; extraction ratio, 0.59 (+/- 0.05). Both studies demonstrate that morphine distribution is rapid and extensive and its t1/2beta relatively short. IM morphine is rapidly and completely absorbed.

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“…Recently, the FDA published a proposal regulating irradiated foods for human consumption (2). The proposal permits irradiation of any food at a dose not >lo0 Krads without the additional safety data.…”

Section: Keyphrases Corticosteroids-wo-irradiated Radiolytic Degradamentioning

confidence: 99%