General Hospital, Bristol I Liver volume and the clearances of antipyrine and indocyanine green have been measured before and after administration of phenobarbitone (180 mg/day) for 3 weeks to ten healthy subjects. 2 The measurement of liver volume by an ultrasound scanning technique yielded reproducible results which were consistent with predictions of liver size by allometric methods. 3 Before phenobarbitone, antipyrine clearance correlated with liver volume, but there was no correlation between indocyanine green clearance and liver volume. 4 Phenobarbitone administration increased the clearance of antipyrine significantly by 90 ± 14% but there was no significant change in indocyanine green clearance or liver volume. 5 After phenobarbitone the correlation between antipyrine clearance and liver volume persisted. There was no correlation between indocyanine green clearance and liver volume. 6 These results suggest that in non-medicated subjects some of the difference in antipyrine clearance is due to difference in functional hepatic parenchymal mass and that phenobarbitone increases the drug metabolising capacity per unit of hepatic mass but not total liver size.

No abstract

The pharmacokinetics, following i.v. administration of (+)‐propranolol (40 mg) have been compared to in vitro measurement of protein binding and biochemical parameters of liver function in six normal subjects and twenty patients with stable chronic liver disease. The clearance of (+)‐ propranolol decreased with evidence of increasing severity of impairment of liver function correlating significantly with a fall in serum albumin, a rise in bilirubin and a prolongation in prothrombin index. The clearance of (+)‐propranolol correlated with and was numerically similar to the clearance of indocyanine green in normal subjects and also in patients with chronic liver disease. Protein binding was decreased in chronic liver disease, but this change was not related to changes in plasma proteins. In normal subjects and patients without ascites the volume of distribution increased with decreases in protein binding. Ascites was associated with a further increase in the volume of distribution. The considerable variation in half‐life largely depends on changes in liver blood flow, the degree of protein binding and the plasma protein pool size.

No abstract

and the Renal Uniit, Royal Infirmary, Cardiff SYNOPSIS Coagulation and platelet function studies were performed on 24 normal subjects and 29 patients with chronic renal failure due to various causes. Thrombocytopenia was uncommon in the uraemic patients but there was reduced platelet retention in glass bead columns and platelet aggregation with adenosine diphosphate (ADP) and thrombin was slower and less complete than normal. The rate of platelet disaggregation in uraemic patients was significantly reduced. The abnormalities tended to be more severe in more uraemic subjects. In normal subjects no interrelationships were observed between the various measurements of platelet activity. In patients there were significant interrelationships between the measurements of platelet aggregation with ADP and thrombin and between the measurements of aggregation and retention in glass bead columns. It is suggested that if a common pathway is involved in these reactions it is adversely affected in uraemia.Plasma coagulation defects were uncommon and present in only five of the uraemic subjects. Impaired prothrombin consumption apparently due to defective platelet function was present in half the patients but was not detected by a kaolin aotivation method. Although platelet coagulation function was activated during ADP aggregation and disaggregation in normal and uraemic subjects, it did not correlate in the latter with impairment of aggregation. It is suggested that aggregation and activation of platelet coagulant activity are not necessarily related aspects of platelet function. An effect of uraemic plasma on normal platelets was demonstrated by mixing experiments consistent with a humoral cause for the uraemic platelet defects.An abnormal bleeding tendency in patients with renal failure has been recognized for many years and has been attributed to several causes. Increased capillary fragility and thrombocytopenia have been described but recent work suggests that in uraemia the platelets do not function properly. In this condition they have been found to adhere abnormally to glass and to aggregate poorly with adenosine diphosphate (ADP) (Castaldi, Rozenberg, and Stewart, 1966) and thrombin Received for publication 31 May 1972. are due to the production of abnormal platelets or to the direct effect of humoral or other factors.In this paper we describe the results of a study of platelet function in chronic renal failure. The platelets of these patients were retained abnormally in glass bead columns and they aggregated poorly with ADP, and especially with tbrombin. Incubation of normal platelets with uraemic plasma resulted in an altered pattern of aggregation with ADP.