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L H Cope

Publications and source records attributed to L H Cope.

7 recordsLinked to original sources

The association of age and frailty with the pharmacokinetics and pharmacodynamics of metoclopramide.

We have investigated the association of age and frailty with the pharmacokinetics and pharmacodynamics of the conjugated drug, metoclopramide. Six healthy young, six healthy elderly (> 65 years), and six frail elderly (> 65 years) subjects were studied on two occasions, receiving 10 mg metoclopramide by intravenous bolus and orally, in random order. Blood and urine were collected for measurement of pharmacokinetic parameters. Liver volume was measured by ultrasound. Sedation and contentment were self-recorded on visual analogue scales. Liver volume was not significantly different in the three groups, nor was bio-availability of metoclopramide. Clearance was similar in the young and fit elderly but reduced in the frail elderly subjects when compared with the young (p < 0.05), both when expressed in absolute terms and per unit liver volume. There were no differences in percentages cleared as the free drug or as the sulphate or glucuronide metabolite within or between groups, suggesting that frailty can produce a general impairment of conjugation pathways. The frail elderly subjects reported more sedation after intravenous dosage than the other subjects, whilst only young subjects reported akathisia. This did not relate to pharmacokinetic differences and seemed therefore to reflect associated pharmacodynamic changes in specific receptor or target sites.

Administration, Oral↗

Case report: lower limb arterial blood supply arising from the renal artery with congenital absence of the ipsilateral iliac arteries.

A case of a young male who developed left lower limb claudication following left nephrectomy is presented. Investigations, including an exploratory laparotomy, demonstrated the absence of left common and internal iliac arteries. An abnormal left external iliac artery arose from the left renal artery and, with collaterals, formed the arterial supply to the lower limb. This anomalous vascular pattern may have caused the pelvi-ureteric junction obstruction which necessitated the nephrectomy. Division of the renal artery at nephrectomy compromised the circulation to the ipsilateral lower limb. Recognition of this anomaly dictates extra caution when dividing the renal artery at nephrectomy performed through a posterolateral approach.

Adult↗

The association of age and frailty with paracetamol conjugation in man.

The association of age, physical frailty and liver size upon hepatic conjugation reactions was studied using paracetamol as a model drug. Nineteen fit subjects (mean age 26 years), 20 fit subjects (mean age 73 years), and eight frail, hospitalized subjects (mean age 82 years) were recruited. Paracetamol clearance expressed in terms of body weight was significantly lower in the fit elderly than in the fit young subjects, and was lowest in the frail elderly subjects (p less than 0.01). There was no difference in paracetamol clearance expressed per unit volume of liver between the fit young and fit elderly subjects but it was significantly reduced in the frail subjects. Although the partial metabolic clearance to paracetamol sulphate was preserved per unit volume of liver with ageing and frailty, the partial metabolic clearance to paracetamol glucuronide per unit volume of liver was markedly reduced in the frail elderly (p less than 0.01) when compared with the fit subjects. These results show that age-associated changes in paracetamol clearance are attributable to both changes in liver volume and in general health. The findings underline the important influences of the elderly person's physical state upon drug clearance.

Acetaminophen↗

The effect of age upon liver volume and apparent liver blood flow in healthy man.

The aim of this study was to determine the effect of aging upon liver volume and apparent liver blood flow in healthy man. Sixty-five subjects between 24 and 91 years of age were recruited. Liver volume was quantitated by a gray scale B ultrasound scan method. Apparent liver blood flow was determined from the plasma clearance of indocyanine green, based on an assumption of no change in hepatic extraction of the dye with age. A significant negative correlation was observed between age and both liver volume and apparent liver blood flow (p less than 0.001), whether expressed in absolute terms or per unit body weight. Similarly, a significant negative correlation was observed between apparent liver blood flow per unit volume of liver (liver perfusion) and age (p less than 0.005). The reduction in liver volume, apparent liver blood flow and perfusion may at least partly account for the decline in the clearance of many drugs undergoing liver metabolism which has been noted to occur with aging in man.

Adult↗

The effect of age and frailty upon acetanilide clearance in man.

Six healthy young subjects (aged 23-32 years), six healthy elderly subjects (over 60 years) and six hospitalized long-stay geriatric subjects over 60 years received single oral doses of acetanilide. Acetanilide clearance was similar in the fit and frail elderly subjects at 26.4 +/- 2.5 and 26.3 +/- 3.6 l/h and significantly lower (p less than 0.05) than in the young subjects at 39.0 +/- 1.9 l/h. Liver volumes, measured by ultrasound, were significantly less in the elderly than in the young subjects, whether expressed in absolute terms or per unit body weight (p less than 0.05). When acetanilide clearance was expressed per unit volume of liver, no change occurred with age or frailty. These results suggest that a reduced liver size may be an important contributor to the reduced elimination of capacity limited drugs in elderly man.

Acetanilides↗