Potential Pulmonary Uptake and Clearance of Morphine in Postoperative Patients

Persson, M. P.; Wiklund, Lars; Hartvig, Per; Paalzow, Lennart

doi:10.1097/00132586-198708000-00037

Cited by 5 publications

(5 citation statements)

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“…Previous pharmacokinetic studies have been performed during continuous intravenous infusion with morphine in postoperative patients with apparently normal hepatic and renal functions (Persson et al, 1986;Tanguy et al, 1987). After correcting for the morphine blood/plasma concentration ratio of 1.1 determined in humans (Patwardhan et al, 1981), the plasma clearance values found in the present study are similar in distribution to the blood clearance values reported by Persson 1986).…”

Section: Discussionsupporting

confidence: 82%

The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive‐care patients.

Milne

Nation

Somogyi

et al. 1992

Brit J Clinical Pharma

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1. The relationships between renal creatinine clearance and the renal clearances of morphine, morphine‐3‐glucuronide (M3G) and morphine‐6‐ glucuronide (M6G) were studied in fifteen intensive‐care patients who were receiving morphine sulphate by constant intravenous infusion and who had diverse renal function. 2. An arterial blood sample was collected before and after a 4‐5 h urine collection. Plasma and urine concentrations of morphine, M3G and M6G were measured by h.p.l.c. Plasma binding of all three compounds in drug‐free plasma from healthy volunteers was determined by ultrafiltration. Measured renal creatinine clearance (CLCr, meas) was calculated from plasma and urinary creatinine concentrations (from h.p.l.c.). Also, creatinine clearance was predicted (CLCr, pred) from routine laboratory determination of plasma creatinine (Jaffe method). 3. There were significant linear relationships (P less than 0.001) between CLCr, meas and the renal clearances of morphine, M3G and M6G. The unbound renal clearance of morphine exceeded CLCr, meas (P less than 0.002) while the unbound renal clearances of M3G and M6G did not differ from CLCr, meas (P greater than 0.5). 4. In ten of the patients who received a constant infusion of morphine for at least 6 h, the dose‐normalised plasma concentrations of M3G and M6G increased with decreasing CLCr, pred. Significant (P less than 0.001) relationships were observed between the reciprocal of CLCr, pred and the dose‐normalised plasma concentrations of M3G and M6G. 5. The results indicate the importance of renal function in determining the renal clearances and plasma concentrations of M3G and M6G during intravenous infusion with morphine in intensive‐care patients.

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Section: Discussionsupporting

confidence: 82%

The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive‐care patients.

Milne

Nation

Somogyi

et al. 1992

Brit J Clinical Pharma

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“…The lung is known to metabolize and take up selectively certain endogenous and exogenous substances [24]. Studies in anaesthetized and postoperative patients showed significant uptake, but no metabolism of morphine [25,26]. Although not metabolically active, the lung is thought to act as a reservoir for morphine and other basic drugs.…”

Section: Discussionmentioning

confidence: 99%

Extrahepatic Morphine Metabolism in Man During the Anhepatic Phase of Orthotopic Liver Transplantation

Bodenham

Quinn

Park

1989

British Journal of Anaesthesia

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The primary site for the metabolism of morphine has been the subject of controversy for some time. We studied morphine metabolism during the anhepatic phase of orthotopic liver transplantation in seven adult patients. After injection of morphine 10 mg at the beginning of this phase, the plasma and urinary concentrations of unchanged morphine, morphine-3-glucuronide, morphine-6-glucuronide and normorphine were measured by high pressure liquid chromatography. Small but measurable concentrations of morphine metabolites were found in the plasma and urine whilst there was no functional liver tissue in the body. Morphine metabolism increased markedly when the new donor liver was reperfused. This suggests that, in these patients, the liver is the primary site for metabolism of morphine.

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“…The lungs are engaged in a variety of nonrespiratory functions. Because of their strategic position in the systemic circulation and their unique anatomical construction, they may make a considerable contribution to the metabolism and accumulation of many endogenous and exogenous compounds [10][11][12]. The local anaesthetic agents bupivacaine, mepivacaine and lignocaine have been shown to accumulate in pulmonary tissue, as do propranolol, morphine, methadone, amphetamine and many other drugs [13].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Kinetics of Fentanyl and Alfentanil in Surgical Patients

Taeger

Weninger

Schmelzer

et al. 1988

British Journal of Anaesthesia

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Lipid-soluble basic drugs may be sequestered as the drug-loaded blood passes through the pulmonary capillaries [1], and the amount of drug remaining in the blood for distribution to the organism may be substantially reduced by this mechanism. The temporary sequestration of a significant proportion of an i.v. dose of a drug by the lung may influence the intensity and duration of its pharmacological effect [2]. Hess, Herz and Friedel [3] reported that rabbit lung had a high affinity for fentanyl: approximately 24 % of the dose administered was sequestered as the drug passed through the lung for the first time ("first pass"). Several reports demonstrated a high fentanyl binding capacity of the human lung [4-7]. This paper describes quantitatively the pulmonary kinetics of fentanyl and alfentanil in patients suffering from coronary artery disease. PATIENTS AND METHODS After approval was granted by the local ethics committee for an investigation into the pulmonary kinetics of fentanyl and alfentanil in surgical patients, informed consent was obtained from 11 patients (10 male) scheduled to undergo elective coronary artery bypass surgery. Patients ranged in age from 36 to 67 yr and in body weight from 71 to 81 kg. They were divided into two groups: fentanyl (five patients; Nos 1-5. No. 5 was the

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Potential Pulmonary Uptake and Clearance of Morphine in Postoperative Patients

Cited by 5 publications

References 0 publications

The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive‐care patients.

The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive‐care patients.

Extrahepatic Morphine Metabolism in Man During the Anhepatic Phase of Orthotopic Liver Transplantation

Pulmonary Kinetics of Fentanyl and Alfentanil in Surgical Patients

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