Determination of drug metabolizing enzymes in needle biopsies of human liver

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.

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

The relationship between liver volume, antipyrine clearance and indocyanine green clearance before and after phenobarbitone administration in man.

Roberts¹,

Jackson²,

Halliwell³

et al. 1976

“…Several groups have reported values for mixed function oxidase activity of human liver, using either microsomal fractions of wedge biopsies (Davies & Thorgeirsson, 1971;Black, Perrett & Carter, 1973), or whole homogenate (Schoene, Fleischmann, Remmer & van Olderhausen, 1972) or postmitochondrial supernatant (Fraser, Williams, Davies, Draffan & Davies, 1976) AHH (pmol min-1 mg-1) Figure 5 Relationship between microsomal cytochrome P-450 content and aryl hydrocarbon hydroxylase (AHH) activity in needle and wedge biopsies of human liver with normal architecture.…”

Section: Discussionmentioning

confidence: 99%

Monooxygenase activity of human liver in microsomal fractions of needle biopsy specimens.

Boobis¹,

Brodie²,

Kahn³

et al. 1980

142

1 Methods are described for the determination of mixed function oxidase activity in microsomal fractions from percutaneous needle biopsies of human liver. 2 Activities of needle biopsy samples were comparable with those of wedge biopsy sample obtained at laparotomy from different subjects. 3 Although cytochrome P‐450 content of liver from rat and man was similar, human AHH activity was only 10% of that in the rat. 4 In biopsies with preserved hepatic architecture, AHH activity and cytochrome P‐450 content showed a significant positive correlation. 5 Cigarette smoking significantly increased both AHH activity and turnover number, but not cytochrome P‐450 content, of biopsies with normal architecture. 6 The presence of liver disease caused a significant decrease in AHH activity and cytochrome P‐450 content.

“…In man, the present status is confusing since either no or poor correlation (May, Helmsteaedt, Bustegens & McLean, 1974;Thorgeirsson, 1971;Davies, Thorgeirsson, Breckenridge & Orme, 1973) or a significant relationship (Remmer et al, 1973) between in vivo and (Sotaniemi, Ahlqvist, Pelkonen, Pirttiaho & Luoma, 1977) clearly demonstrate the necessity to consider two independent factors, namely the alterations in liver parenchyma and the role of exposure to inducing agents when investigating drug metabolism in man. The compounds with enzyme inducing properties enhance the microsomal enzyme activity in the liver, but parenchymal changes, like fatty accumulation, amount of fibrous tissue or inflammatory process might interfere with the amount and activity of the enzyme system (Schoene, Fleishman, Remmer & von Olderhausen, 1972;Sotaniemi et al, 1977) and the microsomal drug hydroxylation changes correspondingly. Furthermore, the liver parenchymal alterations also influence the drug uptake and metabolism in the liver by changing hepatic blood flow, availability of NADPH, drug penetration through the cell membranes or liver size (Wilkinson & Schenker, 1976;Remmer et al, 1973;Pirttiaho, Sotaniemi, Pelkonen, Ahlqvist & Pitkanen, unpublished observations).…”

Section: Calculationsmentioning

confidence: 99%

Drug metabolism in epileptics: in vivo and in vitro correlations.

Ea¹,

Pelkonen²,

Ahokas³

et al. 1978

I The effect of inducing drug therapy on the relationship between in vitro (cytochrome P-450 content) and in vivo (antipyrine kinetics) was investigated by comparing eleven consecutively treated epileptics with two groups of controls, eleven subjects with normal liver histology and eleven disease matched non-epileptics, all underwent diagnostic liver biopsy. 2 The epileptics had significantly higher cytochrome P-450 level in biopsies and they also metabolized antipyrine taster than the controls. 3 Decrease in antipyrine half-life in epileptics was related with alterations in liver histology, whereas the level of cytochrome P-450 was not. 4 There was a linear relationship between these two indices of enzyme induction when regressed on logarithmic data.