Methods of the assessment of the effect of drugs on liver blood flow in man.

Ohnhaus, E. E.

doi:10.1111/j.1365-2125.1979.tb00926.x

Cited by 20 publications

(9 citation statements)

References 48 publications

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“…We have confirmed then that drugs with f3-adrenoceptor blocking actions may cause a reduction in HBF. The only other pharmacological source of variability in hepatic blood flow of which we are aware is the suggested increase associated with hepatic enzyme induction (Ohnhaus, 1979). In previous studies we have been unable to confirm this suggestion and have found variation between enzyme inducing agents in their effect on ICG clearance (Roberts et al, 1976;Jackson.…”

Section: Discussionmentioning

confidence: 91%

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Physiological and pharmacological variability in estimated hepatic blood flow in man.

Daneshmend¹,

Jackson²,

Roberts³

1981

Brit J Clinical Pharma

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1 Changes in hepatic blood flow have been estimated by measurement of single-dose indocyanine green kinetics in groups of healthy individuals. 2 The effects of change in posture, exercise and ingestion of milk on estimated hepatic blood flow have been assessed. 3 The erect posture and exercise significantly decreased ICG clearance. However, no consistent change was noted after ingestion of milk. 4 The effects of the adrenoceptor blocking drugs phenoxybenzamine, propranolol and labetalol on hepatic blood flow were also assessed. 5 Propanolol and labetalol caused a significant fall in ICG clearance in the supine position. Phenoxybenzamine did not show a consistent change. 6 Posture, exercise and adrenoceptor blockade appear to be important variables affecting hepatic blood flow. They should be considered when kinetics of high-clearance drugs are measured, and may provide a useful model for the assessment of the effects of alterations in hepatic blood flow on the clearance of drugs.

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Section: Discussionmentioning

confidence: 91%

“…The methods available for estimation of hepatic blood flow have recently been reviewed (Ohnhaus. 1979).…”

Section: Discussionmentioning

confidence: 99%

Physiological and pharmacological variability in estimated hepatic blood flow in man.

Daneshmend¹,

Jackson²,

Roberts³

1981

Brit J Clinical Pharma

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“…The limb blood flow was measured with strain-gauge plethysmography. The indicator dilution method was used for the evaluation of hepatic blood flow [12,13]: Cardiogreen was injected at a dose of 0.5 mg/kg into the right atrium and blood samples were collected through a peripheral vein at 3-minute intelwals.…”

Section: Methodsmentioning

confidence: 99%

Felodipine in severe chronic congestive heart failure: Acute effects on central hemodynamics and regional blood flow distribution

Binetti

Rubino

Varani

et al. 1989

Cardiovasc Drug Ther

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In order to assess the effect of felodipine, a new calcium antagonist with vascular selectivity, on regional blood flow distribution at rest in chronic congestive heart failure, ten patients were studied during an acute test. Right heart catheterization allowed the evaluation of hemodynamic parameters; renal blood flow was calculated using paraamino-hippuric acid clearance; hepatic blood flow measurement was based on indocyanine green clearance; and limb blood flow was assessed with venous occlusion plethysmography. Blood samples were collected for the analysis of plasma catecholamines, renin, and aldosterone. All parameters were recorded in duplicate under basal conditions and after felodipine infusion. The infusion of felodipine induced a significant increase in cardiac index, stroke work index, and limb blood flow. Systemic and pulmonary arterial blood pressure, pulmonary wedge pressure, and systemic resistance underwent a significant decrease. The heart rate, pulmonary resistance, renal blood flow, and hepatic blood flow were not changed. In conclusion, felodipine was of benefit in congestive heart failure at rest in an acute test, acting through a marked decrease in vascular resistance and a consequent improvement in cardiac output and limb blood flow. No changes in renal and hepatic blood flow were observed.

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“…The hypothesis of some modifications of hepatic blood flow by diclofenac was investigated by using an indirect method, i.e., an ICG test that has been widely used in humans (14). The kinetics of ICG in rabbits have been detailed by Thiessen et al (19).…”

Section: Discussionmentioning

confidence: 99%

Reduction in biliary excretion of ceftriaxone by diclofenac in rabbits

Merle-Melet

Seta

Farinotti

et al. 1989

Antimicrob Agents Chemother

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The effects of diclofenac, a nonsteroidal anti-inflammatory drug, on biliary excretion of ceftriaxone were evaluated in rabbits. In a previous study, we demonstrated that diclofenac increased the extravascular diffusion and antibacterial efficacy of ceftriaxone without any effect on serum protein binding and urinary excretion of this antibiotic. We perfected a surgical procedure that allowed the study of biliary secretion in conscious rabbits with a stable hemodynamic state. The kinetic study was carried out on the fourth day of treatment with ceftriaxone alone (30 mg/kg per day given intramuscularly; group 1) or combined with diclofenac (1.5 mg/kg per 12 h given intramuscularly; group 2). Cumulative biliary excretion of ceftriaxone over 6 h was significantly reduced in group 2 (5,291.6 + 2,017.5 ,ug in group 1 versus 1,379.1 + 567.1 ,ug in group 2). This phenomenon occurred without any change in biliary flow. Indocyanine green clearance (20 mg/kg) increased in animals treated with ceftriaxone alone compared with the saline-treated control group (55.04 ± 4.68 versus 33.29 + 7.52 ml/min per kg, respectively). Diclofenac alone caused a significant decrease in indocyanine green clearance compared with clearance in controls (25.05 ± 4.74 versus 33.29 + 7.52 ml/min per kg), and indocyanine green clearance appeared not significantly different from control values in animals receiving ceftriaxone plus diclofenac. These results suggest that (i) ceftriaxone could increase hepatic blood flow and (ii) reduction of the hepatic clearance of ceftriaxone by diclofenac may be due to hepatic hemodynamic variations involving diclofenac inhibition of prostaglandin synthesis, although an interaction of diclofenac with hepatic uptake of ceftriaxone cannot be ruled out.The use of nonsteroidal anti-inflammatory drugs in the therapy of infectious diseases remains a subject for debate. Recent studies argue for a beneficial effect of cyclooxygenase inhibitors on gross pathology and levels of prostaglandin E2 in Staphylococcus aureus-induced experimental osteomyelitis (17) without any significant effect on the mean counts of S. aureus. Khurana and Deddish (C. M. Khurana ad P. A. is , Pr:am Abstr. 26th Intersci. Conf. Antimicrob. Agents Chemother., abstr. no. 544, 1986) reported that the administration of ibuprofen in conjunction with oxacillin or clindamycin increased the effectiveness of the antibiotic against an oxacillin-tolerant strain of S. aureus in an experimental model of osteomyelitis. These results suggest that prostaglandins may be involved in the pathogenesis of bone infection and that inhibition of their secretion may prevent deleterious lesions and help antibiotic efficacy. In the same respect, Tuomanen et al. (21) studied the effect of diclofenac on the inflammatory response in cerebrospinal fluid during Streptococcus pneumoniae-induced experimental meningitis in rabbits. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and an abnormal cerebrospinal fluid chemistry was prevented by the in...

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Methods of the assessment of the effect of drugs on liver blood flow in man.

Cited by 20 publications

References 48 publications

Physiological and pharmacological variability in estimated hepatic blood flow in man.

Physiological and pharmacological variability in estimated hepatic blood flow in man.

Felodipine in severe chronic congestive heart failure: Acute effects on central hemodynamics and regional blood flow distribution

Reduction in biliary excretion of ceftriaxone by diclofenac in rabbits

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